Conformational dynamics of HIV-1 protease: a comparative molecular dynamics simulation study with multiple amber force fields

Meher, Biswa Ranjan and Kumar, Mattaparthi Venkata Satish and Sharma, Smriti and Bandyopadhyay, Pradipta (2012) Conformational dynamics of HIV-1 protease: a comparative molecular dynamics simulation study with multiple amber force fields. In: Journal of Bioinformatics and Computational Biology, 10 (6). pp. 1250018-1.

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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 er 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.

Item Type:	Journal Article
Publication:	Journal of Bioinformatics and Computational Biology
Publisher:	World Scientific Publishing Company
Additional Information:	Copyright of this article belongs to World Scientific Publishing Company.
Keywords:	Molecular Dynamics; Force Field; S2 Order Parameter; Flap Movement; Exible Binding Site
Department/Centre:	Division of Physical & Mathematical Sciences > Physics
Date Deposited:	15 Feb 2013 10:35
Last Modified:	15 Feb 2013 10:35
URI:	http://eprints.iisc.ac.in/id/eprint/45364

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