Week 1 HW: project ideas
What do you want to make?
→ Custom designed protein; post translational modifications/ usage of nonstandard amino acids (e.g. selenocysteine) not clear.
For the purpose of this homework, may the custom protein be named Cuop. Coup is a peptidic macromolecule I plan to design, analyse and test using various computational tools. Its intended goal is to address prion activity in-vivo; work like an inhibitory drug against prion PrPSc “infectious” folding mechanism. The explanation for a protein’s ability to self-propagate a motif is intermolecular interactions between strongly bound-together amino acids (PrPSc beta sheets) and a less rigid structure (PrP alpha helices). Therefore a molecule able to prevent the interactions between the two proteins may be capable of preventing the spread of disease in high risk patients. The way I aim to achieve this is molecular docking simulations to assess if the custom protein can actually help.
The synthesis of Coup is contextualised for industry-scale (working with software like Kernel and interpreting the data accordingly), though the proposed activity validation route for the drug may revolve around the ideas of batches and limited portions for quality-assessment bottlenecks.
What living system could make it?
→ Assuming a rather simple peptidic structure with no ions attached, E. coli can be used as a model organism as in-silico workflow parameters usually are determined by Escherichia systems. After clarifying the proposed amino acid sequence, BLAST tools could help in seeking homologous sequences, thus an organism already specialised in synthesizing similar enough structures.
*I am noting the fact that the host living system is a really important choice I need to settle down on later in the pipeline: It should properly replicate the computationally validated lucrative structure and refrain from potentially altering it via unintended integration of the product in own metabolic chains or via its intracellular medium; It should express the gene cost and time efficient; The protein’s toxicity to the organism should be minimised; *