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Method to Predict Crowding Effects by Postprocessing Molecular Dynamics Trajectories: Application to the Flap Dynamics of HIV-1 Protease

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Sanbo Qin†, David D. L. Minh‡, J. Andrew McCammon‡ and Huan-Xiang Zhou*†

^† Department of Physics and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306

^‡ Departments of Chemistry and Biochemistry and of Pharmacology, Center for Theoretical Biological Physics, and Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92093-0365

J. Phys. Chem. Lett., 2010, 1 (1), pp 107–110

DOI: 10.1021/jz900023w

Publication Date (Web): November 9, 2009

*To whom correspondence should be addressed. Phone: (850) 645-1336. Fax: (850) 644-7244. E-mail: hzhou4@fsu.edu. §

Note

Biosciences Division, Argonne National Laboratory, Argonne, Illinois 60439, USA.

Section:

Biochemical Methods

Abstract

The internal dynamics of proteins inside of cells may be affected by the crowded intracellular environments. Here, we test a novel approach to simulations of crowding, in which simulations in the absence of crowders are postprocessed to predict crowding effects, against the direct approach of simulations in the presence of crowders. The effects of crowding on the flap dynamics of HIV-1 protease predicted by the postprocessing approach are found to agree well with those calculated by the direct approach. The postprocessing approach presents distinct advantages over the direct approach in terms of accuracy and speed and is expected to have broad impact on atomistic simulations of macromolecular crowding.

Keywords (keywords):

macromolecular crowding; protein dynamics; HIV-1 protease; drug design

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This article has been cited by 3 ACS Journal articles (3 most recent appear below).

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  The Journal of Physical Chemistry B2012 116 (1), 599-605
  The effect of cellular crowding was examined from molecular dynamics simulations of chymotrypsin inhibitor 2 (CI2) in the presence of either lysozyme or bovine serum albumin (BSA) crowder molecules as a complement to recent experimental studies of the ...
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Gating and Intermolecular Interactions in Ligand-Protein Association: Coarse-Grained Modeling of HIV-1 Protease
Myungshim Kang, Christopher Roberts, Yuhui Cheng, and Chia-en A. Chang
Journal of Chemical Theory and Computation2011 7 (10), 3438-3446
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  Myungshim Kang, Christopher Roberts, Yuhui Cheng, and Chia-en A. Chang
  Journal of Chemical Theory and Computation2011 7 (10), 3438-3446
  Most biological processes are initiated or mediated by the association of ligands and proteins. This work studies multistep, ligand–protein association processes by Brownian dynamics simulations with coarse-grained models for HIV-1 protease (HIVp) and its ...
  Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links
Crowding Effects on Protein Association: Effect of Interactions between Crowding Agents
Jun Soo Kim and Arun Yethiraj
The Journal of Physical Chemistry B2011 115 (2), 347-353
- Crowding Effects on Protein Association: Effect of Interactions between Crowding Agents
  Jun Soo Kim and Arun Yethiraj
  The Journal of Physical Chemistry B2011 115 (2), 347-353
  The cell cytoplasm is a dense environment where the presence of inert cosolutes can significantly alter the rates of protein folding and protein association reactions. Most theoretical studies focus on hard sphere crowding agents and quantify the effect ...
  Abstract | Full Text HTML | Hi-Res PDF | PDF w/ Links