Abstract
Binding dynamics and pathways of ligands or inhibitors to target proteins are challenging both experimental and theoretical biologists. A dynamics understanding of inhibitors interacting with protein is essential for the design of novel potent drugs. In this work we applied a coarse-grained molecular dynamics method for simulating inhibitors entering the binding cavity of human immunodeficiency virus type 1 protease (PR). It shows that the coarse-grained dynamics, consistent with the experimental results, can capture the essential molecular dynamics of various inhibitors binding into PR. The primary driving force for the binding processes is the nonbond interaction between inhibitors and PR. The size and topology of inhibitors and the interacting strength between inhibitors and PR have great influence on the binding mode and processes. The interaction strength between the PR and various inhibitors is also analyzed by atomistic molecular mechanics and Poisson-Boltzmann solvation area method.
| Original language | English (US) |
|---|---|
| Article number | 215102 |
| Journal | Journal of Chemical Physics |
| Volume | 130 |
| Issue number | 21 |
| DOIs | |
| State | Published - 2009 |
Funding
The authors thank Professor V. Tozzini, Professor C. E. Chang, Professor J. Trylska, and Professor J. Andrew McCammon for critical discussions and provision of the Morse potential parameters. M.S.L. should acknowledge the support of the Swinburne-Tsinghua Exchange Program and thank discussions with Professor R. J. Sadus and Professor B. D. Todd of Swinburne. B.J. acknowledges the support by the National Natural Science Foundation of China through Grant Nos. 10628205, 10732050, and 10872115 and the National Basic Research Program of China through Grant No. 2007CB936803, and SRF-SEM for ROCS.
ASJC Scopus subject areas
- General Physics and Astronomy
- Physical and Theoretical Chemistry
