title: Conformational dynamics of HIV-1 protease: a comparative molecular dynamics simulation study with multiple amber force fields.
abstract: Flap dynamics of HIV-1 protease (HIV-pr) controls the entry of inhibitors and substrates to the active site. Dynamical models from previous simulations are not all consistent with each other and not all are supported by the NMR results. In the present work, the effect of force field on the dynamics of HIV-pr is investigated by MD simulations using three AMBER force fields ff99, ff99SB, and ff03. The generalized order parameters for amide backbone are calculated from the three force fields and compared with the NMR S2 values. We found that the ff99SB and ff03 force field calculated order parameters agree reasonably well with the NMR S2 values, whereas ff99 calculated values deviate most from the NMR order parameters. Stereochemical geometry of protein models from each force field also agrees well with the remarks from NMR S2 values. However, between ff99SB and ff03, there are several differences, most notably in the loop regions. It is found that these loops are, in general, more flexible in the ff03 force field. This results in a larger active site cavity in the simulation with the ff03 force field. The effect of this difference in computer-aided drug design against flexible receptors is discussed.
authors: Computational Biology Research Laboratory, Department of Biotechnology, Indian Institute of Technology, Guwahati, Assam 781039, India. brmeher@gmail.com
authors: Biswa Ranjan
authors: BR
authors: Meher
authors: Mattaparthi Venkata Satish
authors: MV
authors: Kumar
authors: Smriti
authors: S
authors: Sharma
authors: Pradipta
authors: P
authors: Bandyopadhyay
mesh_terms: D003198:Computer Simulation; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation / Q000592:standards*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation
chemical_list: D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1