title: Molecular dynamic simulation reveals damaging impact of RAC1 F28L mutation in the switch I region.
abstract: Ras-related C3 botulinum toxin substrate 1 (RAC1) is a plasma membrane-associated small GTPase which cycles between the active GTP-bound and inactive GDP-bound states. There is wide range of evidences indicating its active participation in inducing cancer-associated phenotypes. RAC1 F28L mutation (RAC(F28L)) is a fast recycling mutation which has been implicated in several cancer associated cases. In this work we have performed molecular docking and molecular dynamics simulation (~0.3 μs) to investigate the conformational changes occurring in the mutant protein. The RMSD, RMSF and NHbonds results strongly suggested that the loss of native conformation in the Switch I region in RAC1 mutant protein could be the reason behind its oncogenic transformation. The overall results suggested that the mutant protein attained compact conformation as compared to the native. The major impact of mutation was observed in the Switch I region which might be the crucial reason behind the loss of interaction between the guanine ring and F28 residue.
authors.affiliation: Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore, Tamil Nadu, India.
authors.forename: Ambuj
authors.initials: A
authors.lastname: Kumar
authors.forename: Vidya
authors.initials: V
authors.lastname: Rajendran
authors.forename: Rao
authors.initials: R
authors.lastname: Sethumadhavan
authors.forename: Rituraj
authors.initials: R
authors.lastname: Purohit
mesh_terms: D019943:Amino Acid Substitution; D006860:Hydrogen Bonding; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D012997:Solvents / Q000737:chemistry; D020830:rac1 GTP-Binding Protein / Q000737:chemistry* / Q000235:genetics*
chemical_list: D012997:Solvents; D020830:rac1 GTP-Binding Protein