Week 05 HW: Protein Design Part 2

Part A: SOD1 Binder Peptide Design (From Pranam)

  1. SRWDVYAGAVKWARK 10.46594,

    WWVPPYTAVYAWKKK 17.463782,

    SRWGEYVGVYKARAA 12.508359,

    WRVDVVVAVKKAKKK 12.361373,

    while FLYRWLPSRRGG shows perplexity 8.1.

  2. imTM = 0.37, seems to be a random surface and hardly binds.

    imTM = 0.31, a random surface and hardly binds

    imTM = 0.4, dimer interface

    imTM = 0.32, random surface

    imTM = 0.43, dimer interface

The imTM values are small, which returns weak binding. I don’t think that any peptide matches the known binder.

  1. Weak binding, soluble, non-hemolytical, 2.46, 1793 Da

    Weak binding, soluble, non-hemolytical, 2.76, 1923.3 Da

    Weak binding, soluble, non-hemolytical, 1.46, 1712.9 Da

    Weak binding, soluble, non-hemolytical, 4.76, 1754.2 Da

    Weak binding, soluble, non-hemolytical, 2.76, 1507.7 Da

I see a similar pattern regarding week binding, being soluble, and non-hemolytic. The net charge does not seem to play a role in binding. Based on this, it can be predicted that strong binders will be hemolytic and poorly soluble. In theory, higher ipTM should show stronger predicted affinity, but mine are all weak. I don’t have a peptide of strong binding yet.

  1. I failed to generate peptides on moPPit Colab. Theoretically, I believe that the peptides would be stronger because of the specific instructions (binding locations, criteria…). In this way, peptides would be more chemically balanced, less likely to cause toxicity, and better suited for therapeutic development.

Part C: Final Project: L-Protein Mutants

I can’t finish running the notebook, as I get stuck at from google.colab import files. I tried two different networks and spent hours running them, but I can’t continue. Therefore, in the absence of the notebook scores, I expect variations between the experimental data and the scores, as experience and predictions never align perfectly.

The five mutated sequences could be:

  1. Q to E. METRFPQQSQETPASTNRRRPFKHEDYPCRRQQRSSTLYVLIFLAIFLSKFTNQLLLSLLEAVIRTVTTLQQLLT
  2. S to T. METRFPQQSQQTPASTNTRRPFKHEDYPCRRQQRSSTLYVLIFLAIFLSKFTNQLLLSLLEAVIRTVTTLQQLLT
  3. L to I. METRFPQQSQQTPASTNRRRPFKHEDYPCRRQQRSSTLYVLIFIAIFLSKFTNQLLLSLLEAVIRTVTTLQQLLT
  4. F to Y. METRFPQQSQQTPASTNRRRPFKHEDYPCRRQQRSSTLYVLIFLAIYLSKFTNQLLLSLLEAVIRTVTTLQQLLT
  5. V to I. METRFPQQSQQTPASTNRRRPFKHEDYPCRRQQRSSTLYVLIFLAIFLSKFTNQLLLSLLEAIIRTVTTLQQLLT