Week 5: Protein design 2
HOMEWORK
Part A: SOD1 Binder Peptide Design
Context Superoxide dismutase 1 (SOD1) is a cytosolic antioxidant enzyme -protein- that converts superoxide radicals into hydrogen peroxide and oxygen. In its native state, it forms a stable homodimer and binds copper and zinc. Mutations in SOD1 cause familial Amyotrophic Lateral Sclerosis (ALS). Among them, the A4V mutation (Alanine → Valine at residue 4) leads to one of the most aggressive forms of the disease. The mutation subtly destabilizes the N-terminus, perturbs folding energetics, and promotes toxic aggregation.
Your challenge:
1. Design short peptides -aminoacit chain going form 2 to 50 aprox- that bind mutant SOD1.
2. Then decide which ones are worth advancing toward therapy.
What is a peptide binder? short proteins that bind to larger proteins. Peptide binders are high specific and cheap to synthesize. Therefor they are a prime candidate for drug design. In this case to bind -or fix- mutant SOD1.
You will use three models:
-PepMLM: target sequence-conditioned peptide generation via masked language modeling. Here is an opena ccess article for reference: https://www.nature.com/articles/s41587-025-02761-2
-PeptiVerse: therapeutic property prediction. Here is an opena ccess article for reference: https://www.biorxiv.org/content/10.64898/2025.12.31.697180v1.full.pdf
-moPPIt: motif-specific multi-objective peptide design using Multi-Objective Guided Discrete Flow Matching (MOG-DFM). Here is an opena ccess article for reference: https://www.biorxiv.org/content/10.1101/2024.07.31.606098v2
Instructions
Part 1: Generate Binders with PepMLM
-Looking for the PepMLM model I found a webpage called TamarindoBio, wich seems to be very helpfull since integrates different models in one singe platform for computational biology: https://www.tamarind.bio/
Begin by retrieving the human SOD1 sequence from UniProt (P00441)
>sp|P00441|SODC_HUMAN Superoxide dismutase [Cu-Zn] OS=Homo sapiens OX=9606 GN=SOD1 PE=1 SV=2
MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTS AGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVV HEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ
..and introducing the A4V mutation.
sp|P00441|SODC_HUMAN_A4V Superoxide dismutase [Cu-Zn] A4V mutant OS=Homo sapiens MATKVVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTS AGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVV HEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ
Using the PepMLM Colab linked from the HuggingFace PepMLM-650M model card: Generate four peptides of length 12 amino acids conditioned on the mutant SOD1 sequence. To your generated list, add the known SOD1-binding peptide FLYRWLPSRRGG for comparison. Record the perplexity scores that indicate PepMLM’s confidence in the binders.
Binder Perplexity
TRGEDLELLLEGLWG 16.156637 (ATKAVCVLISG a common mutant SOD1 sequence)
index,Binder,Pseudo Perplexity 0,WTRGETEEENWL,20.351590911595604 1,KPRGETTVVNWR,10.28386335939656 2,RTTDDEEVEEPL,13.21296682161187 3,WPTEEEEEEEPL,7.778752281638014 (This is the lowest. Why?)
FLYRWLPSRRGG SOD1 comparion peptide conditioned on the mutant SOD1 sequence provided by the instructor:
index,Binder,Pseudo Perplexity 0,KPEGEEEVEPGE,14.948628502503167 1,RRRDEEPVEEPE,11.433765492062454 2,RREGETPEEPWR,11.150938004006173 3,WTTDEEELEEWR,22.782388379405774 (This is the highest. Why?)
Part 2: Evaluate Binders with AlphaFold3 This model led to the nobel prize winners in chemestry for the 2024. Here is a paper explaining how it works: https://www.nature.com/articles/s41586-024-07487-w
Instructions Navigate to the AlphaFold Server: alphafoldserver.com
For each peptide, submit the mutant SOD1 sequence followed by the peptide sequence as separate chains to model the protein-peptide complex.
Record the ipTM score and briefly describe where the peptide appears to bind.
What is the pTM and the ipTM? In the frequently asked questions of the AlfaFold server I found the following answer: the predicted template modeling (pTM) score and the interface predicted template modeling (ipTM) score are both derived from a measure called the template modeling (TM) score. This measures the accuracy of the entire structure (Zhang and Skolnick, 2004; Xu and Zhang, 2010). A pTM score above 0.5 means the overall predicted fold for the complex might be similar to the true structure. ipTM measures the accuracy of the predicted relative positions of the subunits within the complex. Values higher than 0.8 represent confident high-quality predictions, while values below 0.6 suggest likely a failed prediction. ipTM values between 0.6 and 0.8 are a gray zone where predictions could be correct or incorrect. TM score is very strict for small structures or short chains, so pTM assigns values less than 0.05 when fewer than 20 tokens are involved; for these cases PAE or pLDDT may be more indicative of prediction quality.
Does it localize near the N-terminus where A4V sits?
Does it engage the β-barrel region or approach the dimer interface?
Does it appear surface-bound or partially buried?
In a short paragraph, describe the ipTM values you observe and whether any PepMLM-generated peptide matches or exceeds the known binder.
I used Anthropic Claude trying to understand the results I got running the binnder ranked with the lower Perplexity index (WPTEEEEEEEPL,7.778752281638014) and the higher (WTTDEEELEEWR,22.782388379405774). Not sure why in both cases the ipTM was the same: 0.41. However, the PTM changed a bit, for the former was 0.86 and the later 0.87. I will present Anthropic interpretation only for the higher:
Results Interpretation: WTTDEEELEEWR + SOD1 A4V Scores Received MetricScoreInterpretationipTM0.41⚠️ Low confidence interfacepTM0.87✅ High confidence overall fold
What These Scores Mean pTM = 0.87 ✅
The overall structure prediction is high quality SOD1 A4V is folding correctly and confidently This is expected — SOD1 is a well-characterized protein
ipTM = 0.41 ⚠️
This is the critical score for protein-peptide interaction Falls in the low confidence zone (threshold for reliable interaction is typically >0.60) Suggests the peptide does not form a stable, well-defined complex with SOD1 A4V The binding pose may be ambiguous or non-specific
| ipTM Score Scale Reference | ||||
|---|---|---|---|---|
| 0.0 0.2 0.4 0.6 0.8 1.0 | ||||
| ↑ | ||||
| 0.41 | ||||
| WTTDEEELEEWR | ||||
| (Low/Uncertain) | ||||
| ↑ | ||||
| Strong hit | ||||
| needed here |
Biological Interpretation ObservationImplicationLow ipTM (0.41)Peptide likely does not bind specifically to SOD1 A4VHigh pTM (0.87)SOD1 structure is well-predicted — not a modeling artifactScore near 0.40 cutoffInteraction is borderline — could be weak/transientPeptide character (acidic) May not complement SOD1 surface well at this site. Regarding the N-terminus / A4V Site Question Given the low ipTM of 0.41, you should still check the structure visually, but: The peptide likely does not localize confidently near Val4. Any placement near the N-terminus would be unreliable at this confidence level. The acidic stretch (DEEELEEE) of the peptide may be electrostatically incompatible with the local SOD1 surface near A4V
Summary Statement for Your Report
“The WTTDEEELEEWR peptide yielded an ipTM score of 0.41 against SOD1 A4V, indicating low confidence in the predicted protein-peptide interface. While the overall SOD1 structure was well-modeled (pTM = 0.87), the interaction does not appear to be specific or stable. Visual inspection of the model is needed to determine whether the peptide localizes near the A4V mutation site at the N-terminus, though the low ipTM score suggests this interaction may not be physiologically meaningful.”
What is the difference between the N and the C terminuous? I found a video where is well explained: https://youtu.be/y3G_W-3J_8k. Here is an screean shoot of it:
Part 3: Evaluate Properties of Generated Peptides in the PeptiVerse: https://huggingface.co/spaces/ChatterjeeLab/PeptiVerse
Structural confidence alone is insufficient for therapeutic development. Using PeptiVerse, let’s evaluate the therapeutic properties of your peptide! For each PepMLM-generated peptide:
Intructions: Paste the peptide sequence. Paste the A4V mutant SOD1 sequence in the target field. Check the boxes Predicted binding affinity Solubility Hemolysis probability Net charge (pH 7) Molecular weight
Results:
Compare these predictions to what you observed structurally with AlphaFold3. In a short paragraph, describe what you see. Do peptides with higher ipTM also show stronger predicted affinity? Are any strong binders predicted to be hemolytic or poorly soluble? Which peptide best balances predicted binding and therapeutic properties?
Comparison: AlphaFold3 and PeptiVerse show low affinity for WTTDEEELEEWR + SOD1 A4V. The choosen peptide is soluble, however, is non-hemolytic, maybe the latter characteristic is the reason for its weak binding affinity.
Choose one peptide you would advance and justify your decision briefly.
Non of my designed pepdides showed affinity. Therefore I will procede with WTTDEEELEEWR in order to verify if is posible to optimize it wiht moPPIt.
Part 4: Generate Optimized Peptides with moPPIt
Now, move from sampling to controlled design. moPPIt uses Multi-Objective Guided Discrete Flow Matching (MOG-DFM) to steer peptide generation toward specific residues and optimize binding and therapeutic properties simultaneously. Unlike PepMLM, which samples plausible binders conditioned on just the target sequence, moPPIt lets you choose where you want to bind and optimize multiple objectives at once.
Open the moPPit Colab linked from the HuggingFace moPPIt model card. Make a copy and switch to a GPU runtime. In the notebook: Paste your A4V mutant SOD1 sequence. Choose specific residue indices on SOD1 that you want your peptide to bind (for example, residues near position 4, the dimer interface, or another surface patch). Set peptide length to 12 amino acids. Enable motif and affinity guidance (and solubility/hemolysis guidance if available). Generate peptides.
Results moPPIt-v3 aims to design peptide binders for the A4V mutant SOD1 sequence
/content/moPPIt/flow_matching/path/path_sample.py:45: SyntaxWarning: invalid escape sequence ‘\s’
x_t (Tensor): the sample along the path :math:X_t \sim p_t.
/content/moPPIt/flow_matching/path/scheduler/scheduler.py:72: SyntaxWarning: invalid escape sequence ‘\s’
SchedulerOutput: :math:\alpha_t,\sigma_t,\frac{\partial}{\partial t}\alpha_t,\frac{\partial}{\partial t}\sigma_t
/content/moPPIt/flow_matching/path/scheduler/scheduler.py:79: SyntaxWarning: invalid escape sequence ‘\k’
Computes :math:t from :math:\kappa_t.
Target Motifs: [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]
tensor([ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10], device=‘cuda:0’)
Some weights of EsmModel were not initialized from the model checkpoint at facebook/esm2_t33_650M_UR50D and are newly initialized: [’esm.pooler.dense.bias’, ’esm.pooler.dense.weight’]
You should probably TRAIN this model on a down-stream task to be able to use it for predictions and inference.
Some weights of EsmModel were not initialized from the model checkpoint at facebook/esm2_t33_650M_UR50D and are newly initialized: [’esm.pooler.dense.bias’, ’esm.pooler.dense.weight’]
You should probably TRAIN this model on a down-stream task to be able to use it for predictions and inference.
Some weights of EsmModel were not initialized from the model checkpoint at facebook/esm2_t33_650M_UR50D and are newly initialized: [’esm.pooler.dense.bias’, ’esm.pooler.dense.weight’]
You should probably TRAIN this model on a down-stream task to be able to use it for predictions and inference.
NFE: 0: 0%| | 0/0.9990000128746033 [00:00<?, ?it/s]Weight Vector: tensor([1., 1., 1., 1.], device=‘cuda:0’) [0.892784483730793, 0.4166666269302368, 0.638796865940094, 0.013969388790428638]
NFE: 0: 1%| | 0.009999999776482582/0.9990000128746033 [00:08<13:15, 804.35s/it] NFE: 1: 1%| | 0.009999999776482582/0.9990000128746033 [00:08<13:15, 804.37s/it][0.892784483730793, 0.4166666269302368, 0.638796865940094, 0.013969388790428638]
NFE: 1: 2%|▏ | 0.019999999552965164/0.9990000128746033 [00:13<11:22, 697.17s/it] NFE: 2: 2%|▏ | 0.019999999552965164/0.9990000128746033 [00:13<11:22, 697.18s/it][0.892784483730793, 0.4166666269302368, 0.638796865940094, 0.013969388790428638]
NFE: 2: 3%|▎ | 0.029999999329447746/0.9990000128746033 [00:19<10:43, 664.21s/it] NFE: 3: 3%|▎ | 0.029999999329447746/0.9990000128746033 [00:19<10:43, 664.22s/it][0.892784483730793, 0.4166666269302368, 0.638796865940094, 0.013969388790428638]
NFE: 3: 4%|▍ | 0.03999999910593033/0.9990000128746033 [00:25<10:22, 648.69s/it] NFE: 4: 4%|▍ | 0.03999999910593033/0.9990000128746033 [00:25<10:22, 648.70s/it][0.892784483730793, 0.4166666269302368, 0.638796865940094, 0.013969388790428638]
NFE: 4: 5%|▌ | 0.05000000074505806/0.9990000128746033 [00:31<10:07, 639.74s/it] NFE: 5: 5%|▌ | 0.05000000074505806/0.9990000128746033 [00:31<10:07, 639.74s/it][0.892784483730793, 0.4166666269302368, 0.638796865940094, 0.013969388790428638]
NFE: 5: 6%|▌ | 0.05999999865889549/0.9990000128746033 [00:38<09:56, 635.41s/it] NFE: 6: 6%|▌ | 0.05999999865889549/0.9990000128746033 [00:38<09:56, 635.41s/it][0.892784483730793, 0.4166666269302368, 0.638796865940094, 0.013969388790428638]
NFE: 6: 7%|▋ | 0.07000000029802322/0.9990000128746033 [00:44<09:48, 632.94s/it] NFE: 7: 7%|▋ | 0.07000000029802322/0.9990000128746033 [00:44<09:48, 632.94s/it][0.892784483730793, 0.4166666269302368, 0.638796865940094, 0.013969388790428638]
NFE: 7: 8%|▊ | 0.07999999821186066/0.9990000128746033 [00:50<09:41, 632.33s/it] NFE: 8: 8%|▊ | 0.07999999821186066/0.9990000128746033 [00:50<09:41, 632.34s/it][0.892784483730793, 0.4166666269302368, 0.638796865940094, 0.013969388790428638]
NFE: 8: 9%|▉ | 0.09000000357627869/0.9990000128746033 [00:56<09:35, 632.75s/it] NFE: 9: 9%|▉ | 0.09000000357627869/0.9990000128746033 [00:56<09:35, 632.75s/it][0.892784483730793, 0.4166666269302368, 0.638796865940094, 0.013969388790428638]
NFE: 9: 10%|█ | 0.10000000149011612/0.9990000128746033 [01:03<09:30, 634.08s/it] NFE: 10: 10%|█ | 0.10000000149011612/0.9990000128746033 [01:03<09:30, 634.08s/it]Jump! [0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 10: 11%|█ | 0.10999999940395355/0.9990000128746033 [01:09<09:25, 636.14s/it] NFE: 11: 11%|█ | 0.10999999940395355/0.9990000128746033 [01:09<09:25, 636.15s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 11: 12%|█▏ | 0.11999999731779099/0.9990000128746033 [01:16<09:21, 638.47s/it] NFE: 12: 12%|█▏ | 0.11999999731779099/0.9990000128746033 [01:16<09:21, 638.47s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 12: 13%|█▎ | 0.12999999523162842/0.9990000128746033 [01:23<09:16, 640.18s/it] NFE: 13: 13%|█▎ | 0.12999999523162842/0.9990000128746033 [01:23<09:16, 640.18s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 13: 14%|█▍ | 0.14000000059604645/0.9990000128746033 [01:29<09:11, 642.06s/it] NFE: 14: 14%|█▍ | 0.14000000059604645/0.9990000128746033 [01:29<09:11, 642.06s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 14: 15%|█▌ | 0.15000000596046448/0.9990000128746033 [01:36<09:07, 644.57s/it] NFE: 15: 15%|█▌ | 0.15000000596046448/0.9990000128746033 [01:36<09:07, 644.57s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 15: 16%|█▌ | 0.1599999964237213/0.9990000128746033 [01:43<09:02, 646.56s/it] NFE: 16: 16%|█▌ | 0.1599999964237213/0.9990000128746033 [01:43<09:02, 646.56s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 16: 17%|█▋ | 0.17000000178813934/0.9990000128746033 [01:50<08:57, 648.82s/it] NFE: 17: 17%|█▋ | 0.17000000178813934/0.9990000128746033 [01:50<08:57, 648.82s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 17: 18%|█▊ | 0.18000000715255737/0.9990000128746033 [01:57<08:53, 651.33s/it] NFE: 18: 18%|█▊ | 0.18000000715255737/0.9990000128746033 [01:57<08:53, 651.33s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 18: 19%|█▉ | 0.1899999976158142/0.9990000128746033 [02:04<08:48, 653.85s/it] NFE: 19: 19%|█▉ | 0.1899999976158142/0.9990000128746033 [02:04<08:48, 653.85s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 19: 20%|██ | 0.20000000298023224/0.9990000128746033 [02:11<08:44, 656.49s/it] NFE: 20: 20%|██ | 0.20000000298023224/0.9990000128746033 [02:11<08:44, 656.49s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 20: 21%|██ | 0.20999999344348907/0.9990000128746033 [02:18<08:40, 659.43s/it] NFE: 21: 21%|██ | 0.20999999344348907/0.9990000128746033 [02:18<08:40, 659.43s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 21: 22%|██▏ | 0.2199999988079071/0.9990000128746033 [02:25<08:36, 662.53s/it] NFE: 22: 22%|██▏ | 0.2199999988079071/0.9990000128746033 [02:25<08:36, 662.53s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 22: 23%|██▎ | 0.23000000417232513/0.9990000128746033 [02:33<08:31, 665.46s/it] NFE: 23: 23%|██▎ | 0.23000000417232513/0.9990000128746033 [02:33<08:31, 665.46s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 23: 24%|██▍ | 0.23999999463558197/0.9990000128746033 [02:40<08:27, 668.40s/it] NFE: 24: 24%|██▍ | 0.23999999463558197/0.9990000128746033 [02:40<08:27, 668.40s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 24: 25%|██▌ | 0.25/0.9990000128746033 [02:47<08:22, 671.29s/it]
NFE: 25: 25%|██▌ | 0.25/0.9990000128746033 [02:47<08:22, 671.29s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 25: 26%|██▌ | 0.25999999046325684/0.9990000128746033 [02:55<08:18, 674.24s/it] NFE: 26: 26%|██▌ | 0.25999999046325684/0.9990000128746033 [02:55<08:18, 674.24s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 26: 27%|██▋ | 0.27000001072883606/0.9990000128746033 [03:02<08:13, 677.51s/it] NFE: 27: 27%|██▋ | 0.27000001072883606/0.9990000128746033 [03:02<08:13, 677.51s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 27: 28%|██▊ | 0.2800000011920929/0.9990000128746033 [03:10<08:09, 680.51s/it] NFE: 28: 28%|██▊ | 0.2800000011920929/0.9990000128746033 [03:10<08:09, 680.51s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 28: 29%|██▉ | 0.28999999165534973/0.9990000128746033 [03:18<08:04, 683.26s/it] NFE: 29: 29%|██▉ | 0.28999999165534973/0.9990000128746033 [03:18<08:04, 683.26s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 29: 30%|███ | 0.30000001192092896/0.9990000128746033 [03:25<07:59, 685.75s/it] NFE: 30: 30%|███ | 0.30000001192092896/0.9990000128746033 [03:25<07:59, 685.75s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 30: 31%|███ | 0.3100000023841858/0.9990000128746033 [03:33<07:54, 688.09s/it] NFE: 31: 31%|███ | 0.3100000023841858/0.9990000128746033 [03:33<07:54, 688.09s/it][0.9081721231341362, 0.4166666269302368, 0.6425620913505554, 0.02499234676361084]
NFE: 31: 32%|███▏ | 0.3199999928474426/0.9990000128746033 [03:40<07:48, 690.47s/it] NFE: 32: 32%|███▏ | 0.3199999928474426/0.9990000128746033 [03:40<07:48, 690.47s/it]Jump! [0.9359819367527962, 0.5, 0.6126851439476013, 0.02760450355708599]
NFE: 32: 33%|███▎ | 0.33000001311302185/0.9990000128746033 [03:48<07:43, 692.72s/it] NFE: 33: 33%|███▎ | 0.33000001311302185/0.9990000128746033 [03:48<07:43, 692.73s/it][0.9359819367527962, 0.5, 0.6126851439476013, 0.02760450355708599]
NFE: 33: 34%|███▍ | 0.3400000035762787/0.9990000128746033 [03:56<07:37, 694.96s/it] NFE: 34: 34%|███▍ | 0.3400000035762787/0.9990000128746033 [03:56<07:37, 694.96s/it][0.9359819367527962, 0.5, 0.6126851439476013, 0.02760450355708599]
NFE: 34: 35%|███▌ | 0.3499999940395355/0.9990000128746033 [04:04<07:32, 697.25s/it] NFE: 35: 35%|███▌ | 0.3499999940395355/0.9990000128746033 [04:04<07:32, 697.25s/it]Jump! [0.9591330401599407, 0.5833333134651184, 0.6140442490577698, 0.017495764419436455]
NFE: 35: 36%|███▌ | 0.36000001430511475/0.9990000128746033 [04:11<07:26, 699.51s/it] NFE: 36: 36%|███▌ | 0.36000001430511475/0.9990000128746033 [04:11<07:26, 699.51s/it][0.9591330401599407, 0.5833333134651184, 0.6140442490577698, 0.017495764419436455]
NFE: 36: 37%|███▋ | 0.3700000047683716/0.9990000128746033 [04:19<07:21, 701.78s/it] NFE: 37: 37%|███▋ | 0.3700000047683716/0.9990000128746033 [04:19<07:21, 701.79s/it][0.9591330401599407, 0.5833333134651184, 0.6140442490577698, 0.017495764419436455]
NFE: 37: 38%|███▊ | 0.3799999952316284/0.9990000128746033 [04:27<07:15, 704.10s/it] NFE: 38: 38%|███▊ | 0.3799999952316284/0.9990000128746033 [04:27<07:15, 704.10s/it]Jump! [0.9491959884762764, 0.5833333134651184, 0.6099125742912292, 0.05870214104652405]
NFE: 38: 39%|███▉ | 0.38999998569488525/0.9990000128746033 [04:35<07:10, 706.22s/it] NFE: 39: 39%|███▉ | 0.38999998569488525/0.9990000128746033 [04:35<07:10, 706.22s/it][0.9491959884762764, 0.5833333134651184, 0.6099125742912292, 0.05870214104652405]
NFE: 39: 40%|████ | 0.4000000059604645/0.9990000128746033 [04:43<07:04, 708.33s/it] NFE: 40: 40%|████ | 0.4000000059604645/0.9990000128746033 [04:43<07:04, 708.33s/it][0.9491959884762764, 0.5833333134651184, 0.6099125742912292, 0.05870214104652405]
NFE: 40: 41%|████ | 0.4099999964237213/0.9990000128746033 [04:51<06:58, 710.37s/it] NFE: 41: 41%|████ | 0.4099999964237213/0.9990000128746033 [04:51<06:58, 710.37s/it]Jump! [0.9700631853193045, 0.6666666269302368, 0.6000106930732727, 0.061128463596105576]
NFE: 41: 42%|████▏ | 0.41999998688697815/0.9990000128746033 [04:59<06:52, 712.36s/it] NFE: 42: 42%|████▏ | 0.41999998688697815/0.9990000128746033 [04:59<06:52, 712.36s/it][0.9700631853193045, 0.6666666269302368, 0.6000106930732727, 0.061128463596105576]
NFE: 42: 43%|████▎ | 0.4300000071525574/0.9990000128746033 [05:07<06:46, 714.40s/it] NFE: 43: 43%|████▎ | 0.4300000071525574/0.9990000128746033 [05:07<06:46, 714.40s/it][0.9700631853193045, 0.6666666269302368, 0.6000106930732727, 0.061128463596105576]
NFE: 43: 44%|████▍ | 0.4399999976158142/0.9990000128746033 [05:15<06:40, 716.34s/it] NFE: 44: 44%|████▍ | 0.4399999976158142/0.9990000128746033 [05:15<06:40, 716.34s/it][0.9700631853193045, 0.6666666269302368, 0.6000106930732727, 0.061128463596105576]
NFE: 44: 45%|████▌ | 0.44999998807907104/0.9990000128746033 [05:23<06:34, 718.26s/it] NFE: 45: 45%|████▌ | 0.44999998807907104/0.9990000128746033 [05:23<06:34, 718.26s/it]Jump! [0.9455092027783394, 0.75, 0.6051879525184631, 0.18141452968120575]
NFE: 45: 46%|████▌ | 0.46000000834465027/0.9990000128746033 [05:31<06:28, 720.22s/it] NFE: 46: 46%|████▌ | 0.46000000834465027/0.9990000128746033 [05:31<06:28, 720.22s/it][0.9455092027783394, 0.75, 0.6051879525184631, 0.18141452968120575]
NFE: 46: 47%|████▋ | 0.4699999988079071/0.9990000128746033 [05:39<06:22, 722.14s/it] NFE: 47: 47%|████▋ | 0.4699999988079071/0.9990000128746033 [05:39<06:22, 722.14s/it][0.9455092027783394, 0.75, 0.6051879525184631, 0.18141452968120575]
NFE: 47: 48%|████▊ | 0.47999998927116394/0.9990000128746033 [05:47<06:15, 723.95s/it] NFE: 48: 48%|████▊ | 0.47999998927116394/0.9990000128746033 [05:47<06:15, 723.95s/it][0.9455092027783394, 0.75, 0.6051879525184631, 0.18141452968120575]
NFE: 48: 49%|████▉ | 0.49000000953674316/0.9990000128746033 [05:55<06:09, 725.92s/it] NFE: 49: 49%|████▉ | 0.49000000953674316/0.9990000128746033 [05:55<06:09, 725.92s/it][0.9455092027783394, 0.75, 0.6051879525184631, 0.18141452968120575]
NFE: 49: 50%|█████ | 0.5/0.9990000128746033 [06:03<06:03, 727.76s/it]
NFE: 50: 50%|█████ | 0.5/0.9990000128746033 [06:03<06:03, 727.76s/it][0.9455092027783394, 0.75, 0.6051879525184631, 0.18141452968120575]
NFE: 50: 51%|█████ | 0.5099999904632568/0.9990000128746033 [06:12<05:56, 729.57s/it] NFE: 51: 51%|█████ | 0.5099999904632568/0.9990000128746033 [06:12<05:56, 729.57s/it]Jump! [0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 51: 52%|█████▏ | 0.5199999809265137/0.9990000128746033 [06:20<05:50, 731.48s/it] NFE: 52: 52%|█████▏ | 0.5199999809265137/0.9990000128746033 [06:20<05:50, 731.48s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 52: 53%|█████▎ | 0.5299999713897705/0.9990000128746033 [06:28<05:43, 733.24s/it] NFE: 53: 53%|█████▎ | 0.5299999713897705/0.9990000128746033 [06:28<05:43, 733.24s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 53: 54%|█████▍ | 0.5400000214576721/0.9990000128746033 [06:36<05:37, 734.88s/it] NFE: 54: 54%|█████▍ | 0.5400000214576721/0.9990000128746033 [06:36<05:37, 734.88s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 54: 55%|█████▌ | 0.550000011920929/0.9990000128746033 [06:45<05:30, 736.60s/it] NFE: 55: 55%|█████▌ | 0.550000011920929/0.9990000128746033 [06:45<05:30, 736.60s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 55: 56%|█████▌ | 0.5600000023841858/0.9990000128746033 [06:53<05:24, 738.18s/it] NFE: 56: 56%|█████▌ | 0.5600000023841858/0.9990000128746033 [06:53<05:24, 738.18s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 56: 57%|█████▋ | 0.5699999928474426/0.9990000128746033 [07:01<05:17, 739.60s/it] NFE: 57: 57%|█████▋ | 0.5699999928474426/0.9990000128746033 [07:01<05:17, 739.60s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 57: 58%|█████▊ | 0.5799999833106995/0.9990000128746033 [07:09<05:10, 741.10s/it] NFE: 58: 58%|█████▊ | 0.5799999833106995/0.9990000128746033 [07:09<05:10, 741.10s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 58: 59%|█████▉ | 0.5899999737739563/0.9990000128746033 [07:18<05:03, 742.45s/it] NFE: 59: 59%|█████▉ | 0.5899999737739563/0.9990000128746033 [07:18<05:03, 742.45s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 59: 60%|██████ | 0.6000000238418579/0.9990000128746033 [07:26<04:56, 743.72s/it] NFE: 60: 60%|██████ | 0.6000000238418579/0.9990000128746033 [07:26<04:56, 743.72s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 60: 61%|██████ | 0.6100000143051147/0.9990000128746033 [07:34<04:49, 745.04s/it] NFE: 61: 61%|██████ | 0.6100000143051147/0.9990000128746033 [07:34<04:49, 745.04s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 61: 62%|██████▏ | 0.6200000047683716/0.9990000128746033 [07:42<04:42, 746.27s/it] NFE: 62: 62%|██████▏ | 0.6200000047683716/0.9990000128746033 [07:42<04:42, 746.27s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 62: 63%|██████▎ | 0.6299999952316284/0.9990000128746033 [07:50<04:35, 747.42s/it] NFE: 63: 63%|██████▎ | 0.6299999952316284/0.9990000128746033 [07:50<04:35, 747.42s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 63: 64%|██████▍ | 0.6399999856948853/0.9990000128746033 [07:59<04:28, 748.62s/it] NFE: 64: 64%|██████▍ | 0.6399999856948853/0.9990000128746033 [07:59<04:28, 748.62s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 64: 65%|██████▌ | 0.6499999761581421/0.9990000128746033 [08:07<04:21, 749.72s/it] NFE: 65: 65%|██████▌ | 0.6499999761581421/0.9990000128746033 [08:07<04:21, 749.72s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 65: 66%|██████▌ | 0.6600000262260437/0.9990000128746033 [08:15<04:14, 750.77s/it] NFE: 66: 66%|██████▌ | 0.6600000262260437/0.9990000128746033 [08:15<04:14, 750.77s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 66: 67%|██████▋ | 0.6700000166893005/0.9990000128746033 [08:23<04:07, 751.93s/it] NFE: 67: 67%|██████▋ | 0.6700000166893005/0.9990000128746033 [08:23<04:07, 751.93s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 67: 68%|██████▊ | 0.6800000071525574/0.9990000128746033 [08:31<04:00, 752.93s/it] NFE: 68: 68%|██████▊ | 0.6800000071525574/0.9990000128746033 [08:31<04:00, 752.93s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 68: 69%|██████▉ | 0.6899999976158142/0.9990000128746033 [08:40<03:52, 753.87s/it] NFE: 69: 69%|██████▉ | 0.6899999976158142/0.9990000128746033 [08:40<03:52, 753.87s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 69: 70%|███████ | 0.699999988079071/0.9990000128746033 [08:48<03:45, 754.83s/it] NFE: 70: 70%|███████ | 0.699999988079071/0.9990000128746033 [08:48<03:45, 754.83s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 70: 71%|███████ | 0.7099999785423279/0.9990000128746033 [08:56<03:38, 755.76s/it] NFE: 71: 71%|███████ | 0.7099999785423279/0.9990000128746033 [08:56<03:38, 755.76s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 71: 72%|███████▏ | 0.7200000286102295/0.9990000128746033 [09:04<03:31, 756.65s/it] NFE: 72: 72%|███████▏ | 0.7200000286102295/0.9990000128746033 [09:04<03:31, 756.65s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 72: 73%|███████▎ | 0.7300000190734863/0.9990000128746033 [09:13<03:23, 757.55s/it] NFE: 73: 73%|███████▎ | 0.7300000190734863/0.9990000128746033 [09:13<03:23, 757.55s/it][0.970262885093689, 0.75, 0.5938253998756409, 0.25562453269958496]
NFE: 73: 74%|███████▍ | 0.7400000095367432/0.9990000128746033 [09:21<03:16, 758.41s/it] NFE: 74: 74%|███████▍ | 0.7400000095367432/0.9990000128746033 [09:21<03:16, 758.41s/it]Jump! [0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 74: 75%|███████▌ | 0.75/0.9990000128746033 [09:29<03:09, 759.20s/it]
NFE: 75: 75%|███████▌ | 0.75/0.9990000128746033 [09:29<03:09, 759.20s/it][0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 75: 76%|███████▌ | 0.7599999904632568/0.9990000128746033 [09:37<03:01, 760.03s/it] NFE: 76: 76%|███████▌ | 0.7599999904632568/0.9990000128746033 [09:37<03:01, 760.03s/it][0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 76: 77%|███████▋ | 0.7699999809265137/0.9990000128746033 [09:45<02:54, 760.79s/it] NFE: 77: 77%|███████▋ | 0.7699999809265137/0.9990000128746033 [09:45<02:54, 760.79s/it][0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 77: 78%|███████▊ | 0.7799999713897705/0.9990000128746033 [09:53<02:46, 761.52s/it] NFE: 78: 78%|███████▊ | 0.7799999713897705/0.9990000128746033 [09:53<02:46, 761.52s/it][0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 78: 79%|███████▉ | 0.7900000214576721/0.9990000128746033 [10:02<02:39, 762.29s/it] NFE: 79: 79%|███████▉ | 0.7900000214576721/0.9990000128746033 [10:02<02:39, 762.29s/it][0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 79: 80%|████████ | 0.800000011920929/0.9990000128746033 [10:10<02:31, 763.00s/it] NFE: 80: 80%|████████ | 0.800000011920929/0.9990000128746033 [10:10<02:31, 763.00s/it][0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 80: 81%|████████ | 0.8100000023841858/0.9990000128746033 [10:18<02:24, 763.70s/it] NFE: 81: 81%|████████ | 0.8100000023841858/0.9990000128746033 [10:18<02:24, 763.70s/it][0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 81: 82%|████████▏ | 0.8199999928474426/0.9990000128746033 [10:26<02:16, 764.41s/it] NFE: 82: 82%|████████▏ | 0.8199999928474426/0.9990000128746033 [10:26<02:16, 764.41s/it][0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 82: 83%|████████▎ | 0.8299999833106995/0.9990000128746033 [10:35<02:09, 765.08s/it] NFE: 83: 83%|████████▎ | 0.8299999833106995/0.9990000128746033 [10:35<02:09, 765.08s/it][0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 83: 84%|████████▍ | 0.8399999737739563/0.9990000128746033 [10:43<02:01, 765.72s/it] NFE: 84: 84%|████████▍ | 0.8399999737739563/0.9990000128746033 [10:43<02:01, 765.72s/it][0.9535586945712566, 0.75, 0.6404362320899963, 0.2548507750034332]
NFE: 84: 85%|████████▌ | 0.8500000238418579/0.9990000128746033 [10:51<01:54, 766.37s/it] NFE: 85: 85%|████████▌ | 0.8500000238418579/0.9990000128746033 [10:51<01:54, 766.38s/it]Jump! [0.9505688734352589, 0.75, 0.648702085018158, 0.3036421239376068]
NFE: 85: 86%|████████▌ | 0.8600000143051147/0.9990000128746033 [10:59<01:46, 766.97s/it] NFE: 86: 86%|████████▌ | 0.8600000143051147/0.9990000128746033 [10:59<01:46, 766.97s/it][0.9505688734352589, 0.75, 0.648702085018158, 0.3036421239376068]
NFE: 86: 87%|████████▋ | 0.8700000047683716/0.9990000128746033 [11:07<01:39, 767.56s/it] NFE: 87: 87%|████████▋ | 0.8700000047683716/0.9990000128746033 [11:07<01:39, 767.56s/it][0.9505688734352589, 0.75, 0.648702085018158, 0.3036421239376068]
NFE: 87: 88%|████████▊ | 0.8799999952316284/0.9990000128746033 [11:15<01:31, 768.17s/it] NFE: 88: 88%|████████▊ | 0.8799999952316284/0.9990000128746033 [11:15<01:31, 768.17s/it]Jump! [0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 88: 89%|████████▉ | 0.8899999856948853/0.9990000128746033 [11:24<01:23, 768.74s/it] NFE: 89: 89%|████████▉ | 0.8899999856948853/0.9990000128746033 [11:24<01:23, 768.74s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 89: 90%|█████████ | 0.8999999761581421/0.9990000128746033 [11:32<01:16, 769.29s/it] NFE: 90: 90%|█████████ | 0.8999999761581421/0.9990000128746033 [11:32<01:16, 769.29s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 90: 91%|█████████ | 0.9100000262260437/0.9990000128746033 [11:40<01:08, 769.83s/it] NFE: 91: 91%|█████████ | 0.9100000262260437/0.9990000128746033 [11:40<01:08, 769.83s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 91: 92%|█████████▏| 0.9200000166893005/0.9990000128746033 [11:48<01:00, 770.35s/it] NFE: 92: 92%|█████████▏| 0.9200000166893005/0.9990000128746033 [11:48<01:00, 770.35s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 92: 93%|█████████▎| 0.9300000071525574/0.9990000128746033 [11:56<00:53, 770.87s/it] NFE: 93: 93%|█████████▎| 0.9300000071525574/0.9990000128746033 [11:56<00:53, 770.87s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 93: 94%|█████████▍| 0.9399999976158142/0.9990000128746033 [12:05<00:45, 771.38s/it] NFE: 94: 94%|█████████▍| 0.9399999976158142/0.9990000128746033 [12:05<00:45, 771.38s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 94: 95%|█████████▌| 0.949999988079071/0.9990000128746033 [12:13<00:37, 771.86s/it] NFE: 95: 95%|█████████▌| 0.949999988079071/0.9990000128746033 [12:13<00:37, 771.86s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 95: 96%|█████████▌| 0.9599999785423279/0.9990000128746033 [12:21<00:30, 772.33s/it] NFE: 96: 96%|█████████▌| 0.9599999785423279/0.9990000128746033 [12:21<00:30, 772.33s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 96: 97%|█████████▋| 0.9700000286102295/0.9990000128746033 [12:29<00:22, 772.82s/it] NFE: 97: 97%|█████████▋| 0.9700000286102295/0.9990000128746033 [12:29<00:22, 772.82s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 97: 98%|█████████▊| 0.9800000190734863/0.9990000128746033 [12:37<00:14, 773.27s/it] NFE: 98: 98%|█████████▊| 0.9800000190734863/0.9990000128746033 [12:37<00:14, 773.27s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 98: 99%|█████████▉| 0.9900000095367432/0.9990000128746033 [12:45<00:06, 773.72s/it] NFE: 99: 99%|█████████▉| 0.9900000095367432/0.9990000128746033 [12:45<00:06, 773.72s/it][0.931668795645237, 0.75, 0.645549476146698, 0.3713146150112152]
NFE: 99: 100%|██████████| 0.9990000128746033/0.9990000128746033 [12:46<00:00, 767.09s/it] NFE: 100: 100%|██████████| 0.9990000128746033/0.9990000128746033 [12:46<00:00, 767.09s/it] NFE: 100: 100%|██████████| 0.9990000128746033/0.9990000128746033 [12:46<00:00, 767.09s/it] 2026-04-12 12:15:43.585473: E external/local_xla/xla/stream_executor/cuda/cuda_fft.cc:467] Unable to register cuFFT factory: Attempting to register factory for plugin cuFFT when one has already been registered WARNING: All log messages before absl::InitializeLog() is called are written to STDERR E0000 00:00:1775996143.819521 8847 cuda_dnn.cc:8579] Unable to register cuDNN factory: Attempting to register factory for plugin cuDNN when one has already been registered E0000 00:00:1775996143.879429 8847 cuda_blas.cc:1407] Unable to register cuBLAS factory: Attempting to register factory for plugin cuBLAS when one has already been registered W0000 00:00:1775996144.365984 8847 computation_placer.cc:177] computation placer already registered. Please check linkage and avoid linking the same target more than once. W0000 00:00:1775996144.366062 8847 computation_placer.cc:177] computation placer already registered. Please check linkage and avoid linking the same target more than once. W0000 00:00:1775996144.366066 8847 computation_placer.cc:177] computation placer already registered. Please check linkage and avoid linking the same target more than once. W0000 00:00:1775996144.366069 8847 computation_placer.cc:177] computation placer already registered. Please check linkage and avoid linking the same target more than once. 2026-04-12 12:15:44.415070: I tensorflow/core/platform/cpu_feature_guard.cc:210] This TensorFlow binary is optimized to use available CPU instructions in performance-critical operations. To enable the following instructions: AVX2 AVX512F FMA, in other operations, rebuild TensorFlow with the appropriate compiler flags. [‘KCWKQKSFGKEI’] [0.931668795645237, 0.75, 6.4554948806762695, 0.3713146150112152]
NFE: 0: 0%| | 0/0.9990000128746033 [00:00<?, ?it/s]Weight Vector: tensor([1., 1., 1., 1.], device=‘cuda:0’) [0.8901347517967224, 0.5, 0.677069365978241, 0.13011868298053741]
NFE: 0: 1%| | 0.009999999776482582/0.9990000128746033 [00:07<12:56, 785.27s/it] NFE: 1: 1%| | 0.009999999776482582/0.9990000128746033 [00:07<12:56, 785.29s/it][0.8901347517967224, 0.5, 0.677069365978241, 0.13011868298053741]
NFE: 1: 2%|▏ | 0.019999999552965164/0.9990000128746033 [00:16<13:04, 801.76s/it] NFE: 2: 2%|▏ | 0.019999999552965164/0.9990000128746033 [00:16<13:04, 801.77s/it][0.8901347517967224, 0.5, 0.677069365978241, 0.13011868298053741]
NFE: 2: 3%|▎ | 0.029999999329447746/0.9990000128746033 [00:24<13:18, 824.22s/it] NFE: 3: 3%|▎ | 0.029999999329447746/0.9990000128746033 [00:24<13:18, 824.23s/it][0.8901347517967224, 0.5, 0.677069365978241, 0.13011868298053741]
NFE: 3: 4%|▍ | 0.03999999910593033/0.9990000128746033 [00:33<13:24, 839.16s/it] NFE: 4: 4%|▍ | 0.03999999910593033/0.9990000128746033 [00:33<13:24, 839.17s/it][0.8901347517967224, 0.5, 0.677069365978241, 0.13011868298053741]
NFE: 4: 5%|▌ | 0.05000000074505806/0.9990000128746033 [00:42<13:18, 841.70s/it] NFE: 5: 5%|▌ | 0.05000000074505806/0.9990000128746033 [00:42<13:18, 841.71s/it][0.8901347517967224, 0.5, 0.677069365978241, 0.13011868298053741]
NFE: 5: 6%|▌ | 0.05999999865889549/0.9990000128746033 [00:50<13:07, 838.97s/it] NFE: 6: 6%|▌ | 0.05999999865889549/0.9990000128746033 [00:50<13:07, 838.98s/it][0.8901347517967224, 0.5, 0.677069365978241, 0.13011868298053741]
NFE: 6: 7%|▋ | 0.07000000029802322/0.9990000128746033 [00:58<12:55, 834.26s/it] NFE: 7: 7%|▋ | 0.07000000029802322/0.9990000128746033 [00:58<12:55, 834.26s/it][0.8901347517967224, 0.5, 0.677069365978241, 0.13011868298053741]
NFE: 7: 8%|▊ | 0.07999999821186066/0.9990000128746033 [01:06<12:41, 828.72s/it] NFE: 8: 8%|▊ | 0.07999999821186066/0.9990000128746033 [01:06<12:41, 828.73s/it][0.8901347517967224, 0.5, 0.677069365978241, 0.13011868298053741]
NFE: 8: 9%|▉ | 0.09000000357627869/0.9990000128746033 [01:14<12:29, 824.62s/it] NFE: 9: 9%|▉ | 0.09000000357627869/0.9990000128746033 [01:14<12:29, 824.63s/it]Jump! [0.9169070199131966, 0.5833333134651184, 0.687084972858429, 0.21130578219890594]
NFE: 9: 10%|█ | 0.10000000149011612/0.9990000128746033 [01:22<12:18, 821.00s/it] NFE: 10: 10%|█ | 0.10000000149011612/0.9990000128746033 [01:22<12:18, 821.00s/it][0.9169070199131966, 0.5833333134651184, 0.687084972858429, 0.21130578219890594]
NFE: 10: 11%|█ | 0.10999999940395355/0.9990000128746033 [01:30<12:08, 819.41s/it] NFE: 11: 11%|█ | 0.10999999940395355/0.9990000128746033 [01:30<12:08, 819.41s/it]Jump! [0.9597424864768982, 0.6666666269302368, 0.6564245820045471, 0.2247355729341507]
NFE: 11: 12%|█▏ | 0.11999999731779099/0.9990000128746033 [01:38<12:01, 820.36s/it] NFE: 12: 12%|█▏ | 0.11999999731779099/0.9990000128746033 [01:38<12:01, 820.36s/it][0.9597424864768982, 0.6666666269302368, 0.6564245820045471, 0.2247355729341507]
NFE: 12: 13%|█▎ | 0.12999999523162842/0.9990000128746033 [01:46<11:54, 822.24s/it] NFE: 13: 13%|█▎ | 0.12999999523162842/0.9990000128746033 [01:46<11:54, 822.24s/it][0.9597424864768982, 0.6666666269302368, 0.6564245820045471, 0.2247355729341507]
NFE: 13: 14%|█▍ | 0.14000000059604645/0.9990000128746033 [01:55<11:47, 823.41s/it] NFE: 14: 14%|█▍ | 0.14000000059604645/0.9990000128746033 [01:55<11:47, 823.41s/it][0.9597424864768982, 0.6666666269302368, 0.6564245820045471, 0.2247355729341507]
NFE: 14: 15%|█▌ | 0.15000000596046448/0.9990000128746033 [02:03<11:39, 823.99s/it] NFE: 15: 15%|█▌ | 0.15000000596046448/0.9990000128746033 [02:03<11:39, 823.99s/it][0.9597424864768982, 0.6666666269302368, 0.6564245820045471, 0.2247355729341507]
NFE: 15: 16%|█▌ | 0.1599999964237213/0.9990000128746033 [02:11<11:30, 823.43s/it] NFE: 16: 16%|█▌ | 0.1599999964237213/0.9990000128746033 [02:11<11:30, 823.43s/it][0.9597424864768982, 0.6666666269302368, 0.6564245820045471, 0.2247355729341507]
NFE: 16: 17%|█▋ | 0.17000000178813934/0.9990000128746033 [02:19<11:21, 822.50s/it] NFE: 17: 17%|█▋ | 0.17000000178813934/0.9990000128746033 [02:19<11:21, 822.51s/it]Jump! [0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 17: 18%|█▊ | 0.18000000715255737/0.9990000128746033 [02:27<11:13, 821.96s/it] NFE: 18: 18%|█▊ | 0.18000000715255737/0.9990000128746033 [02:27<11:13, 821.96s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 18: 19%|█▉ | 0.1899999976158142/0.9990000128746033 [02:36<11:04, 821.33s/it] NFE: 19: 19%|█▉ | 0.1899999976158142/0.9990000128746033 [02:36<11:04, 821.33s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 19: 20%|██ | 0.20000000298023224/0.9990000128746033 [02:44<10:55, 820.89s/it] NFE: 20: 20%|██ | 0.20000000298023224/0.9990000128746033 [02:44<10:55, 820.89s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 20: 21%|██ | 0.20999999344348907/0.9990000128746033 [02:52<10:47, 820.99s/it] NFE: 21: 21%|██ | 0.20999999344348907/0.9990000128746033 [02:52<10:47, 820.99s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 21: 22%|██▏ | 0.2199999988079071/0.9990000128746033 [03:00<10:39, 821.12s/it] NFE: 22: 22%|██▏ | 0.2199999988079071/0.9990000128746033 [03:00<10:39, 821.12s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 22: 23%|██▎ | 0.23000000417232513/0.9990000128746033 [03:08<10:31, 821.32s/it] NFE: 23: 23%|██▎ | 0.23000000417232513/0.9990000128746033 [03:08<10:31, 821.32s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 23: 24%|██▍ | 0.23999999463558197/0.9990000128746033 [03:17<10:23, 821.76s/it] NFE: 24: 24%|██▍ | 0.23999999463558197/0.9990000128746033 [03:17<10:23, 821.76s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 24: 25%|██▌ | 0.25/0.9990000128746033 [03:25<10:15, 821.83s/it]
NFE: 25: 25%|██▌ | 0.25/0.9990000128746033 [03:25<10:15, 821.83s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 25: 26%|██▌ | 0.25999999046325684/0.9990000128746033 [03:33<10:07, 821.64s/it] NFE: 26: 26%|██▌ | 0.25999999046325684/0.9990000128746033 [03:33<10:07, 821.64s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 26: 27%|██▋ | 0.27000001072883606/0.9990000128746033 [03:41<09:58, 821.51s/it] NFE: 27: 27%|██▋ | 0.27000001072883606/0.9990000128746033 [03:41<09:58, 821.51s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 27: 28%|██▊ | 0.2800000011920929/0.9990000128746033 [03:49<09:50, 821.18s/it] NFE: 28: 28%|██▊ | 0.2800000011920929/0.9990000128746033 [03:49<09:50, 821.18s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 28: 29%|██▉ | 0.28999999165534973/0.9990000128746033 [03:58<09:41, 820.75s/it] NFE: 29: 29%|██▉ | 0.28999999165534973/0.9990000128746033 [03:58<09:41, 820.75s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 29: 30%|███ | 0.30000001192092896/0.9990000128746033 [04:06<09:33, 820.49s/it] NFE: 30: 30%|███ | 0.30000001192092896/0.9990000128746033 [04:06<09:33, 820.49s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 30: 31%|███ | 0.3100000023841858/0.9990000128746033 [04:14<09:25, 820.26s/it] NFE: 31: 31%|███ | 0.3100000023841858/0.9990000128746033 [04:14<09:25, 820.26s/it][0.96054982021451, 0.75, 0.6622058749198914, 0.1855875551700592]
NFE: 31: 32%|███▏ | 0.3199999928474426/0.9990000128746033 [04:22<09:16, 820.11s/it] NFE: 32: 32%|███▏ | 0.3199999928474426/0.9990000128746033 [04:22<09:16, 820.12s/it]Jump! [0.9668035097420216, 0.75, 0.6637393832206726, 0.4622972905635834]
NFE: 32: 33%|███▎ | 0.33000001311302185/0.9990000128746033 [04:30<09:08, 820.21s/it] NFE: 33: 33%|███▎ | 0.33000001311302185/0.9990000128746033 [04:30<09:08, 820.22s/it][0.9668035097420216, 0.75, 0.6637393832206726, 0.4622972905635834]
NFE: 33: 34%|███▍ | 0.3400000035762787/0.9990000128746033 [04:38<09:00, 820.34s/it] NFE: 34: 34%|███▍ | 0.3400000035762787/0.9990000128746033 [04:38<09:00, 820.34s/it][0.9668035097420216, 0.75, 0.6637393832206726, 0.4622972905635834]
NFE: 34: 35%|███▌ | 0.3499999940395355/0.9990000128746033 [04:47<08:52, 820.43s/it] NFE: 35: 35%|███▌ | 0.3499999940395355/0.9990000128746033 [04:47<08:52, 820.43s/it][0.9668035097420216, 0.75, 0.6637393832206726, 0.4622972905635834]
NFE: 35: 36%|███▌ | 0.36000001430511475/0.9990000128746033 [04:55<08:44, 820.70s/it] NFE: 36: 36%|███▌ | 0.36000001430511475/0.9990000128746033 [04:55<08:44, 820.70s/it][0.9668035097420216, 0.75, 0.6637393832206726, 0.4622972905635834]
NFE: 36: 37%|███▋ | 0.3700000047683716/0.9990000128746033 [05:03<08:36, 820.85s/it] NFE: 37: 37%|███▋ | 0.3700000047683716/0.9990000128746033 [05:03<08:36, 820.85s/it][0.9668035097420216, 0.75, 0.6637393832206726, 0.4622972905635834]
NFE: 37: 38%|███▊ | 0.3799999952316284/0.9990000128746033 [05:11<08:28, 820.82s/it] NFE: 38: 38%|███▊ | 0.3799999952316284/0.9990000128746033 [05:11<08:28, 820.83s/it][0.9668035097420216, 0.75, 0.6637393832206726, 0.4622972905635834]
NFE: 38: 39%|███▉ | 0.38999998569488525/0.9990000128746033 [05:20<08:19, 820.81s/it] NFE: 39: 39%|███▉ | 0.38999998569488525/0.9990000128746033 [05:20<08:19, 820.81s/it][0.9668035097420216, 0.75, 0.6637393832206726, 0.4622972905635834]
NFE: 39: 40%|████ | 0.4000000059604645/0.9990000128746033 [05:28<08:11, 820.70s/it] NFE: 40: 40%|████ | 0.4000000059604645/0.9990000128746033 [05:28<08:11, 820.70s/it]Jump! [0.975235465914011, 0.75, 0.645666778087616, 0.5373403429985046]
NFE: 40: 41%|████ | 0.4099999964237213/0.9990000128746033 [05:36<08:03, 820.45s/it] NFE: 41: 41%|████ | 0.4099999964237213/0.9990000128746033 [05:36<08:03, 820.45s/it][0.975235465914011, 0.75, 0.645666778087616, 0.5373403429985046]
NFE: 41: 42%|████▏ | 0.41999998688697815/0.9990000128746033 [05:44<07:54, 820.24s/it] NFE: 42: 42%|████▏ | 0.41999998688697815/0.9990000128746033 [05:44<07:54, 820.24s/it][0.975235465914011, 0.75, 0.645666778087616, 0.5373403429985046]
NFE: 42: 43%|████▎ | 0.4300000071525574/0.9990000128746033 [05:52<07:46, 819.95s/it] NFE: 43: 43%|████▎ | 0.4300000071525574/0.9990000128746033 [05:52<07:46, 819.95s/it][0.975235465914011, 0.75, 0.645666778087616, 0.5373403429985046]
NFE: 43: 44%|████▍ | 0.4399999976158142/0.9990000128746033 [06:00<07:38, 819.69s/it] NFE: 44: 44%|████▍ | 0.4399999976158142/0.9990000128746033 [06:00<07:38, 819.69s/it][0.975235465914011, 0.75, 0.645666778087616, 0.5373403429985046]
NFE: 44: 45%|████▌ | 0.44999998807907104/0.9990000128746033 [06:08<07:29, 819.60s/it] NFE: 45: 45%|████▌ | 0.44999998807907104/0.9990000128746033 [06:08<07:29, 819.60s/it][0.975235465914011, 0.75, 0.645666778087616, 0.5373403429985046]
NFE: 45: 46%|████▌ | 0.46000000834465027/0.9990000128746033 [06:17<07:21, 819.62s/it] NFE: 46: 46%|████▌ | 0.46000000834465027/0.9990000128746033 [06:17<07:21, 819.62s/it]Jump! [0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 46: 47%|████▋ | 0.4699999988079071/0.9990000128746033 [06:25<07:13, 819.81s/it] NFE: 47: 47%|████▋ | 0.4699999988079071/0.9990000128746033 [06:25<07:13, 819.81s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 47: 48%|████▊ | 0.47999998927116394/0.9990000128746033 [06:33<07:05, 820.09s/it] NFE: 48: 48%|████▊ | 0.47999998927116394/0.9990000128746033 [06:33<07:05, 820.09s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 48: 49%|████▉ | 0.49000000953674316/0.9990000128746033 [06:41<06:57, 820.26s/it] NFE: 49: 49%|████▉ | 0.49000000953674316/0.9990000128746033 [06:41<06:57, 820.26s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 49: 50%|█████ | 0.5/0.9990000128746033 [06:50<06:49, 820.31s/it]
NFE: 50: 50%|█████ | 0.5/0.9990000128746033 [06:50<06:49, 820.31s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 50: 51%|█████ | 0.5099999904632568/0.9990000128746033 [06:58<06:41, 820.32s/it] NFE: 51: 51%|█████ | 0.5099999904632568/0.9990000128746033 [06:58<06:41, 820.32s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 51: 52%|█████▏ | 0.5199999809265137/0.9990000128746033 [07:06<06:32, 820.17s/it] NFE: 52: 52%|█████▏ | 0.5199999809265137/0.9990000128746033 [07:06<06:32, 820.17s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 52: 53%|█████▎ | 0.5299999713897705/0.9990000128746033 [07:14<06:24, 820.00s/it] NFE: 53: 53%|█████▎ | 0.5299999713897705/0.9990000128746033 [07:14<06:24, 820.01s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 53: 54%|█████▍ | 0.5400000214576721/0.9990000128746033 [07:22<06:16, 819.85s/it] NFE: 54: 54%|█████▍ | 0.5400000214576721/0.9990000128746033 [07:22<06:16, 819.85s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 54: 55%|█████▌ | 0.550000011920929/0.9990000128746033 [07:30<06:08, 819.66s/it] NFE: 55: 55%|█████▌ | 0.550000011920929/0.9990000128746033 [07:30<06:08, 819.66s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 55: 56%|█████▌ | 0.5600000023841858/0.9990000128746033 [07:38<05:59, 819.60s/it] NFE: 56: 56%|█████▌ | 0.5600000023841858/0.9990000128746033 [07:38<05:59, 819.60s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 56: 57%|█████▋ | 0.5699999928474426/0.9990000128746033 [07:47<05:51, 819.55s/it] NFE: 57: 57%|█████▋ | 0.5699999928474426/0.9990000128746033 [07:47<05:51, 819.56s/it][0.9651095755398273, 0.8333333134651184, 0.6414575576782227, 0.6047300696372986]
NFE: 57: 58%|█████▊ | 0.5799999833106995/0.9990000128746033 [07:55<05:43, 819.51s/it] NFE: 58: 58%|█████▊ | 0.5799999833106995/0.9990000128746033 [07:55<05:43, 819.51s/it]Jump! [0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 58: 59%|█████▉ | 0.5899999737739563/0.9990000128746033 [08:03<05:35, 819.51s/it] NFE: 59: 59%|█████▉ | 0.5899999737739563/0.9990000128746033 [08:03<05:35, 819.51s/it][0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 59: 60%|██████ | 0.6000000238418579/0.9990000128746033 [08:11<05:27, 819.57s/it] NFE: 60: 60%|██████ | 0.6000000238418579/0.9990000128746033 [08:11<05:27, 819.57s/it][0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 60: 61%|██████ | 0.6100000143051147/0.9990000128746033 [08:19<05:18, 819.58s/it] NFE: 61: 61%|██████ | 0.6100000143051147/0.9990000128746033 [08:19<05:18, 819.58s/it][0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 61: 62%|██████▏ | 0.6200000047683716/0.9990000128746033 [08:28<05:10, 819.59s/it] NFE: 62: 62%|██████▏ | 0.6200000047683716/0.9990000128746033 [08:28<05:10, 819.59s/it][0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 62: 63%|██████▎ | 0.6299999952316284/0.9990000128746033 [08:36<05:02, 819.67s/it] NFE: 63: 63%|██████▎ | 0.6299999952316284/0.9990000128746033 [08:36<05:02, 819.67s/it][0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 63: 64%|██████▍ | 0.6399999856948853/0.9990000128746033 [08:44<04:54, 819.68s/it] NFE: 64: 64%|██████▍ | 0.6399999856948853/0.9990000128746033 [08:44<04:54, 819.68s/it][0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 64: 65%|██████▌ | 0.6499999761581421/0.9990000128746033 [08:52<04:46, 819.71s/it] NFE: 65: 65%|██████▌ | 0.6499999761581421/0.9990000128746033 [08:52<04:46, 819.71s/it][0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 65: 66%|██████▌ | 0.6600000262260437/0.9990000128746033 [09:01<04:37, 819.78s/it] NFE: 66: 66%|██████▌ | 0.6600000262260437/0.9990000128746033 [09:01<04:37, 819.78s/it][0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 66: 67%|██████▋ | 0.6700000166893005/0.9990000128746033 [09:09<04:29, 819.81s/it] NFE: 67: 67%|██████▋ | 0.6700000166893005/0.9990000128746033 [09:09<04:29, 819.81s/it][0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 67: 68%|██████▊ | 0.6800000071525574/0.9990000128746033 [09:17<04:21, 819.88s/it] NFE: 68: 68%|██████▊ | 0.6800000071525574/0.9990000128746033 [09:17<04:21, 819.88s/it][0.9542454034090042, 0.8333333134651184, 0.6302789449691772, 0.6639485359191895]
NFE: 68: 69%|██████▉ | 0.6899999976158142/0.9990000128746033 [09:25<04:13, 820.01s/it] NFE: 69: 69%|██████▉ | 0.6899999976158142/0.9990000128746033 [09:25<04:13, 820.01s/it]Jump! [0.9441252425312996, 0.8333333134651184, 0.6416442394256592, 0.7646965384483337]
NFE: 69: 70%|███████ | 0.699999988079071/0.9990000128746033 [09:34<04:05, 820.05s/it] NFE: 70: 70%|███████ | 0.699999988079071/0.9990000128746033 [09:34<04:05, 820.05s/it][0.9441252425312996, 0.8333333134651184, 0.6416442394256592, 0.7646965384483337]
NFE: 70: 71%|███████ | 0.7099999785423279/0.9990000128746033 [09:42<03:57, 820.10s/it] NFE: 71: 71%|███████ | 0.7099999785423279/0.9990000128746033 [09:42<03:57, 820.10s/it][0.9441252425312996, 0.8333333134651184, 0.6416442394256592, 0.7646965384483337]
NFE: 71: 72%|███████▏ | 0.7200000286102295/0.9990000128746033 [09:50<03:48, 820.20s/it] NFE: 72: 72%|███████▏ | 0.7200000286102295/0.9990000128746033 [09:50<03:48, 820.20s/it][0.9441252425312996, 0.8333333134651184, 0.6416442394256592, 0.7646965384483337]
NFE: 72: 73%|███████▎ | 0.7300000190734863/0.9990000128746033 [09:58<03:40, 820.25s/it] NFE: 73: 73%|███████▎ | 0.7300000190734863/0.9990000128746033 [09:58<03:40, 820.25s/it][0.9441252425312996, 0.8333333134651184, 0.6416442394256592, 0.7646965384483337]
NFE: 73: 74%|███████▍ | 0.7400000095367432/0.9990000128746033 [10:07<03:32, 820.31s/it] NFE: 74: 74%|███████▍ | 0.7400000095367432/0.9990000128746033 [10:07<03:32, 820.31s/it][0.9441252425312996, 0.8333333134651184, 0.6416442394256592, 0.7646965384483337]
NFE: 74: 75%|███████▌ | 0.75/0.9990000128746033 [10:15<03:24, 820.39s/it]
NFE: 75: 75%|███████▌ | 0.75/0.9990000128746033 [10:15<03:24, 820.39s/it]Jump!
[0.9627367667853832, 0.8333333134651184, 0.6244744658470154, 0.7934784293174744]
NFE: 75: 76%|███████▌ | 0.7599999904632568/0.9990000128746033 [10:23<03:16, 820.46s/it] NFE: 76: 76%|███████▌ | 0.7599999904632568/0.9990000128746033 [10:23<03:16, 820.46s/it][0.9627367667853832, 0.8333333134651184, 0.6244744658470154, 0.7934784293174744]
NFE: 76: 77%|███████▋ | 0.7699999809265137/0.9990000128746033 [10:31<03:07, 820.52s/it] NFE: 77: 77%|███████▋ | 0.7699999809265137/0.9990000128746033 [10:31<03:07, 820.52s/it][0.9627367667853832, 0.8333333134651184, 0.6244744658470154, 0.7934784293174744]
NFE: 77: 78%|███████▊ | 0.7799999713897705/0.9990000128746033 [10:40<02:59, 820.58s/it] NFE: 78: 78%|███████▊ | 0.7799999713897705/0.9990000128746033 [10:40<02:59, 820.58s/it][0.9627367667853832, 0.8333333134651184, 0.6244744658470154, 0.7934784293174744]
NFE: 78: 79%|███████▉ | 0.7900000214576721/0.9990000128746033 [10:48<02:51, 820.59s/it] NFE: 79: 79%|███████▉ | 0.7900000214576721/0.9990000128746033 [10:48<02:51, 820.59s/it][0.9627367667853832, 0.8333333134651184, 0.6244744658470154, 0.7934784293174744]
NFE: 79: 80%|████████ | 0.800000011920929/0.9990000128746033 [10:56<02:43, 820.59s/it] NFE: 80: 80%|████████ | 0.800000011920929/0.9990000128746033 [10:56<02:43, 820.59s/it][0.9627367667853832, 0.8333333134651184, 0.6244744658470154, 0.7934784293174744]
NFE: 80: 81%|████████ | 0.8100000023841858/0.9990000128746033 [11:04<02:35, 820.64s/it] NFE: 81: 81%|████████ | 0.8100000023841858/0.9990000128746033 [11:04<02:35, 820.64s/it][0.9627367667853832, 0.8333333134651184, 0.6244744658470154, 0.7934784293174744]
NFE: 81: 82%|████████▏ | 0.8199999928474426/0.9990000128746033 [11:12<02:26, 820.68s/it] NFE: 82: 82%|████████▏ | 0.8199999928474426/0.9990000128746033 [11:12<02:26, 820.68s/it][0.9627367667853832, 0.8333333134651184, 0.6244744658470154, 0.7934784293174744]
NFE: 82: 83%|████████▎ | 0.8299999833106995/0.9990000128746033 [11:21<02:18, 820.71s/it] NFE: 83: 83%|████████▎ | 0.8299999833106995/0.9990000128746033 [11:21<02:18, 820.71s/it][0.9627367667853832, 0.8333333134651184, 0.6244744658470154, 0.7934784293174744]
NFE: 83: 84%|████████▍ | 0.8399999737739563/0.9990000128746033 [11:29<02:10, 820.78s/it] NFE: 84: 84%|████████▍ | 0.8399999737739563/0.9990000128746033 [11:29<02:10, 820.78s/it]Jump! [0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 84: 85%|████████▌ | 0.8500000238418579/0.9990000128746033 [11:37<02:02, 820.83s/it] NFE: 85: 85%|████████▌ | 0.8500000238418579/0.9990000128746033 [11:37<02:02, 820.83s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 85: 86%|████████▌ | 0.8600000143051147/0.9990000128746033 [11:45<01:54, 820.84s/it] NFE: 86: 86%|████████▌ | 0.8600000143051147/0.9990000128746033 [11:45<01:54, 820.84s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 86: 87%|████████▋ | 0.8700000047683716/0.9990000128746033 [11:54<01:45, 820.89s/it] NFE: 87: 87%|████████▋ | 0.8700000047683716/0.9990000128746033 [11:54<01:45, 820.89s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 87: 88%|████████▊ | 0.8799999952316284/0.9990000128746033 [12:02<01:37, 820.91s/it] NFE: 88: 88%|████████▊ | 0.8799999952316284/0.9990000128746033 [12:02<01:37, 820.91s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 88: 89%|████████▉ | 0.8899999856948853/0.9990000128746033 [12:10<01:29, 820.89s/it] NFE: 89: 89%|████████▉ | 0.8899999856948853/0.9990000128746033 [12:10<01:29, 820.89s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 89: 90%|█████████ | 0.8999999761581421/0.9990000128746033 [12:18<01:21, 820.87s/it] NFE: 90: 90%|█████████ | 0.8999999761581421/0.9990000128746033 [12:18<01:21, 820.87s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 90: 91%|█████████ | 0.9100000262260437/0.9990000128746033 [12:26<01:13, 820.83s/it] NFE: 91: 91%|█████████ | 0.9100000262260437/0.9990000128746033 [12:26<01:13, 820.83s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 91: 92%|█████████▏| 0.9200000166893005/0.9990000128746033 [12:35<01:04, 820.76s/it] NFE: 92: 92%|█████████▏| 0.9200000166893005/0.9990000128746033 [12:35<01:04, 820.76s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 92: 93%|█████████▎| 0.9300000071525574/0.9990000128746033 [12:43<00:56, 820.72s/it] NFE: 93: 93%|█████████▎| 0.9300000071525574/0.9990000128746033 [12:43<00:56, 820.72s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 93: 94%|█████████▍| 0.9399999976158142/0.9990000128746033 [12:51<00:48, 820.67s/it] NFE: 94: 94%|█████████▍| 0.9399999976158142/0.9990000128746033 [12:51<00:48, 820.67s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 94: 95%|█████████▌| 0.949999988079071/0.9990000128746033 [12:59<00:40, 820.62s/it] NFE: 95: 95%|█████████▌| 0.949999988079071/0.9990000128746033 [12:59<00:40, 820.62s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 95: 96%|█████████▌| 0.9599999785423279/0.9990000128746033 [13:07<00:32, 820.59s/it] NFE: 96: 96%|█████████▌| 0.9599999785423279/0.9990000128746033 [13:07<00:32, 820.59s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 96: 97%|█████████▋| 0.9700000286102295/0.9990000128746033 [13:15<00:23, 820.54s/it] NFE: 97: 97%|█████████▋| 0.9700000286102295/0.9990000128746033 [13:15<00:23, 820.54s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 97: 98%|█████████▊| 0.9800000190734863/0.9990000128746033 [13:24<00:15, 820.53s/it] NFE: 98: 98%|█████████▊| 0.9800000190734863/0.9990000128746033 [13:24<00:15, 820.53s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 98: 99%|█████████▉| 0.9900000095367432/0.9990000128746033 [13:32<00:07, 820.55s/it] NFE: 99: 99%|█████████▉| 0.9900000095367432/0.9990000128746033 [13:32<00:07, 820.55s/it][0.9706986900418997, 0.8333333134651184, 0.6235334277153015, 0.7975792288780212]
NFE: 99: 100%|██████████| 0.9990000128746033/0.9990000128746033 [13:32<00:00, 813.53s/it] NFE: 100: 100%|██████████| 0.9990000128746033/0.9990000128746033 [13:32<00:00, 813.53s/it] NFE: 100: 100%|██████████| 0.9990000128746033/0.9990000128746033 [13:32<00:00, 813.53s/it] [‘RLTCDTKQIKQY’] [0.9706986900418997, 0.8333333134651184, 6.235334396362305, 0.7975792288780212]
After generation, briefly describe how these moPPit peptides differ from your PepMLM peptides. How would you evaluate these peptides before advancing them to clinical studies?
I asked Gemini IA linked to the Colab notebook to answere the question got the folloging answere:
How would you evaluate these peptides before advancing them to clinical studies?
Evaluating peptides before advancing them to clinical studies involves a rigorous multi-step process to ensure safety, efficacy, and suitability for human use. Based on the properties optimized by moPPIt-v3, here’s a general approach:
Confirmation of moPPIt-v3 Optimized Properties (In Vitro & Early In Vivo):
Binding Affinity and Specificity: Thoroughly validate the binding affinity to the target and specificity against off-targets using techniques like SPR (Surface Plasmon Resonance), ITC (Isothermal Titration Calorimetry), ELISA, or competitive binding assays.
Motif Binding: If a specific motif is targeted, confirm its interaction and functional consequence.
Solubility and Stability: Assess solubility in various physiological buffers and evaluate stability (e.g., against proteolysis, aggregation) over time and under different environmental conditions.
Hemolysis and Cytotoxicity: Conduct in vitro assays (e.g., red blood cell lysis, cell viability assays) to confirm low or no hemolytic and cytotoxic effects, which moPPIt-v3 aims to minimize.
Non-Fouling: Evaluate the peptide's resistance to non-specific binding to surfaces or other biomolecules, particularly if it's designed for use in complex biological environments or materials.
Half-Life (Early PK): Begin preliminary in vivo pharmacokinetic (PK) studies in animal models to understand the peptide's absorption, distribution, metabolism, and excretion (ADME) profile, especially its circulating half-life, which moPPIt-v3 aims to optimize.
Comprehensive Safety Assessment:
General Toxicology: Conduct acute, sub-acute, and chronic toxicity studies in relevant animal models to identify any adverse effects.
Immunogenicity: Assess the potential for the peptide to elicit an immune response (antibody formation) in preclinical models, which could lead to reduced efficacy or adverse reactions.
Genotoxicity and Carcinogenicity: Evaluate if the peptide can cause DNA damage or has carcinogenic potential, usually through in vitro and in vivo tests.
Efficacy and Pharmacodynamics (PD):
In Vitro Efficacy: Confirm biological activity in cell-based assays or tissue models that mimic the disease state.
In Vivo Efficacy: Demonstrate the therapeutic effect of the peptide in relevant animal models of the target disease. This includes dose-response studies and evaluation of appropriate biomarkers.
Mechanism of Action (MoA): Fully elucidate how the peptide exerts its therapeutic effect.
Formulation and Delivery:
Develop a Stable Formulation: Design a pharmaceutical formulation that ensures the peptide's stability, bioavailability, and appropriate route of administration (e.g., injection, oral, topical).
Manufacturing Feasibility: Ensure the peptide can be produced at scale with consistent quality and purity.
Regulatory Considerations:
GLP/GMP Compliance: All preclinical studies (safety and efficacy) must be conducted under Good Laboratory Practice (GLP) regulations, and manufacturing processes must adhere to Good Manufacturing Practice (GMP) standards.
IND-Enabling Studies: Compile all the necessary data and documentation to support an Investigational New Drug (IND) application to regulatory authorities (e.g., FDA in the US, EMA in Europe), which is required before human clinical trials can commence.
By systematically addressing these points, researchers can build a strong case for a peptide’s potential and mitigate risks before it enters the expensive and complex clinical trial phases.