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


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.


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

Personalised recommendations