Protein-protein interaction and in silico mutagenesis studies on IL17A and its peptide inhibitor.

Protein-protein interactions of Interleukin-17 (IL17) play vital role in the autoimmune and inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, and psoriasis. Potent therapeutics for these diseases could be developed by blocking or modulating these interactions through biologics, peptide inhibitors and small molecule inhibitors. Unlike biologics, peptide inhibitors are cost effective and can be orally available. Peptide inhibitors do not require a binding groove as that of small molecules either. Therefore, crystal structure of IL17A in complex with a high affinity peptide inhibitor (HAP) (1-IHVTIPADLWDWIN-14) is investigated with an aim to find hot spots that could improve its potency. An in silico mutagenesis strategy was implemented using FoldX PSSM to scan for positions tolerant to amino acid substitution. Three positions T4, A7, and N14 showed improved stability when mutated with 'F/M/Y', 'P' and 'F/M/Y', respectively. A set of 31 mutant peptides are designed through combinations of these tolerant mutations using Build Model application of FoldX. Binding affinity and interactions of 31 peptides are assessed through protein-peptide docking and binding free energy calculations. Two peptides namely, P1 ("1-IHVTIP SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02856-y.