Comparative molecular dynamics simulation analysis of G20 and C92 mutations in c-di-GMP I riboswitch and the wild type with docked c-di-GMP ligand

• Published in: Bioinformation Vol. 17; no. 8; pp. 721 - 726
• Main Authors: Kumari, Priyanka, Som, Anup
• Format: Journal Article
• Language: English
• Published: Singapore Biomedical Informatics 31.08.2021
• Subjects: Aptamers; Coordination compounds; Gene expression; Hydrogen bonding; Hydrogen bonds; Ligands; Molecular dynamics; Mutants; Mutation; Residues; Riboswitches; Simulation; Simulation analysis; Therapeutic targets; MD simulation; hydrogen bonding; Binding free energy; Molecular docking; Riboswitch-ligand complexes
• ISSN: 0973-2063; 0973-8894; 0973-2063
• DOI: 10.6026/97320630017721

Riboswitch, a bacterial regulatory RNA consists of an aptamer (specific ligand binding unit) and an expression platform (gene expression modulation unit), which act as a potential drug target as it regulates critical genes. Therefore, it is of interest to glean information on the binding of c-di-GMP ligand to mutated conserved G20 and C92 residues of cyclic diguanosine monophosphate I (c-di-GMP I) riboswitch using molecular dynamics simulation. The result shows that the binding energy of wild/native type riboswitch-ligand complex (3IRW) is lower than the mutant complexes suggesting that the binding affinity for c-di-GMP ligand decreases in case of mutant riboswitches. The hydrogen bonding interactions analysis also showed a high number of hydrogen bonds formation in the wild type riboswitch-ligand complex as compared to the mutant complexes illustrating stronger interaction of ligand to wild type riboswitch than the mutants. The simulation result shows that the mutations affected riboswitch-ligand interactions. The residues G14, G21, C46, A47, and U92 were identified as the key residues which contributed effectively to the binding of c-di-GMP I riboswitch with the natural ligand.