Impact of point mutation P29S in RAC1 on tumorigenesis

• DOI: 10.1007/s13277-016-5329-y
• Publication Date: 2016-10-03T01:15:58Z
• Authors: Vidya Rajendran; Chandrasekhar Gop...; Rituraj Purohit
• Keywords: Models, Molecular; rac1 GTP-Binding Protein; 0301 basic medicine; Skin Neoplasms; Protein Conformation; Molecular Dynamics Simulation; 3. Good health; 03 medical and health sciences; Cell Transformation, Neoplastic; Humans; Point Mutation; Mutant Proteins; Melanoma

A point mutation (P29S) in the RAS-related C3 botulinum toxin substrate 1 (RAC1) was considered to be a trigger for melanoma, form of skin cancer with highest mortality rate. In this study, we have investigated pathogenic role P29S based on conformational behavior RAC1 protein toward guanosine triphosphate (GTP). Molecular interaction, molecular dynamics trajectory analysis (RMSD, RMSF, Rg, SASA, DSSP, and PCA), shape binding pocket were performed analyze interaction energy dynamic native mutant at atomic level. Due mutation, switch I region acquired more flexibility and, compensate it, II becomes rigid their space, as result which GTP increased. The overall results strongly implied that changes conformation regions significant reason its malignant transformation tumorigenesis. We raised opportunity researchers design possible therapeutic molecule by considering our findings.