Chinese Science Bulletin

, Volume 55, Issue 24, pp 2677–2683

Molecular dynamics simulations exploring drug resistance in HIV-1 proteases

Article Bioinformatics

DOI: 10.1007/s11434-010-3257-6

Cite this article as:
Gu, H., Chen, H., Wei, D. et al. Chin. Sci. Bull. (2010) 55: 2677. doi:10.1007/s11434-010-3257-6

Abstract

Although HIV-1 subtype B still dominates the epidemic AIDS in developed countries, an increasing number of people in developing countries are suffering from an epidemic of non-subtype B viruses. What is worse, the efficacy of the combinational use of antiretroviral drugs is gradually compromised by the rapid development of drug resistance. To gain an insight into drug resistance, 10-ns MD simulations were simultaneously conducted on the complexes of the TL-3 inhibitor with 4 different proteases (Bwt, Bmut, Fwt and Fmut), among which the complex of the Bwt protease with the TL-3 inhibitor was treated as the control group. Detailed analyses of MD data indicated that the drug resistance of Bmut against TL-3 mainly derived from loss of an important hydrogen bond and that of Fwt was caused by the decrease of hydrophobic interactions in S1/S1’ pocket, while both of the two reasons mentioned above were the cause of the Fmut protease’s resistance. These results are in good agreement with the previous experiments, revealing a possible mechanism of drug resistance for the aforementioned protease subtypes against the TL-3 inhibitor. Additionally, another indication was obtained that the mutations of M36I, V82A and L90M may induce structural transforms so as to alter the inhibitor’s binding mode.

Keywords

HIV-1 protease drug resistance hydrophobic interactions hydrogen bonds molecular dynamics simulations 

Copyright information

© Science China Press and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.College of Life Sciences and BiotechnologyShanghai Jiaotong UniversityShanghaiChina
  2. 2.Shanghai Centre for Systems BiomedicineShanghai Jiaotong UniversityShanghaiChina
  3. 3.Shanghai Centre for Bioinformation TechnologyShanghaiChina

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