title: Studies on flexibility and binding affinity of Asp25 of HIV-1 protease mutants.
abstract: We have investigated and highlighted the behavior of binding residue, Asp25 by computational analysis, which play an important role in understanding docking process with drug molecule, Ritonavir (Norvir) and the flexibility nature of the Human Immunodeficiency Virus-1 (HIV-1) protease enzyme. It is well known that Ritonavir is a potent and a selective HIV-1 protease inhibitor. Molecular dockings were performed in order to gain insights regarding the binding mode of this inhibitor. In our analysis, we observed Ritonavir had different rank orders of scores against different mutant of this enzyme. Asp25 of the enzyme was found to be the active site for all the mutants. The results clearly suggest that Ritonavir is not able to appropriately bind at the active site of each HIV-1 protease mutant due to RMSD difference of the amino acid (Asp) at the position 25 of all mutants. These findings support the concept that 3D space of active site is a qualitative assessment for binding affinity of inhibitor with an enzyme. The investigation on the flexibility nature of Asp25 by normal mode analysis, show that binding residue posses less flexibility due to its solvation potential. The overall analysis of our study brings clarity to the binding behavior with respect to the different mutants with Ritonavir on the basis RMSD and also on the flexible nature of HIV-1 protease enzyme with respect to Asp25 position.
authors: School of Biotechnology, Chemical and Biomedical Engineering, Bioinformatics Division, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India.
authors: Rituraj
authors: R
authors: Purohit
authors: R
authors: R
authors: Rajasekaran
authors: C
authors: C
authors: Sudandiradoss
authors: C
authors: C
authors: George Priya Doss
authors: K
authors: K
authors: Ramanathan
authors: Sethumadhavan
authors: S
authors: Rao
mesh_terms: D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000737:chemistry*; D001665:Binding Sites; D016333:HIV Protease / Q000737:chemistry* / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000235:genetics*; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D019438:Ritonavir / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D012997:Solvents / Q000737:chemistry
chemical_list: D017320:HIV Protease Inhibitors; D012997:Solvents; D001224:Aspartic Acid; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; D019438:Ritonavir