Molecular Dynamic Simulation and Docking of Cyclophilin A Mutants with its Potential Inhibitors

Abstract

Background and objectives: Cyclophilin A (CypA) is involved in various human biological processes. Its role in many pathological conditions makes it a promising target for treating human diseases, such as viral infections. The aim of the present study was to investigate docking of CypA mutants with its potential inhibitors using molecular dynamic simulation ((MDS). Methods: The crystallographic structure of CypA was extracted from the protein database (PDB). Important CypA substitutions were obtained from the literature. CypA inhibitors were taken from chemical databases. The affinity and binding sites of the compounds to CypA and its mutants were also scaled through Autodock Vina. Root-mean-square deviation (RMSD), radios gyration, Lenard-jones potential, and hydrogen bonding were investigated by using MDS for 600 ps. Results: The findings revealed that SangfA and HBF-0259 had more affinity to the CypA (-7.8Kcal/mol and -7.5Kcal/mol, respectively). Conformational changes were observed in CypA W121A/F mutants. SangfA complexed with CypA and its mutants had relatively stable RMSD. Higher Lenard-Jones potential has been observed in the interaction of SangfA to W121A, HBF-0259 to M61, and SCY-635 to H70F. The SangfA had a higher HBs ratio with CypA. Conclusion: Given the higher affinity of SangfA and HBF-0259 to CypA and its mutants, they would influence the stability of the protein. RMSD analysis revealed that SangfA is probably ligated to CypA and its mutants, which are relatively stable. Substitution at W121 residue would reduce inhibitor binding to CypA.

Keywords

• hbf-0259
• cyclophilin a
• sanglifehrin a
• cypa inhibitors
• molecular dynamic simulation