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Molecular dynamics simulations exploring drug resistance in HIV-1 proteases

  • Article
  • Bioinformatics
  • Published:
Chinese Science Bulletin

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 (B wt, B mut, F wt and F mut), among which the complex of the B wt protease with the TL-3 inhibitor was treated as the control group. Detailed analyses of MD data indicated that the drug resistance of B mut against TL-3 mainly derived from loss of an important hydrogen bond and that of F wt 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 F mut 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.

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Authors and Affiliations

  1. College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, 200240, China

    Hui Gu, HaiFeng Chen & DongQing Wei

  2. Shanghai Centre for Systems Biomedicine, Shanghai Jiaotong University, Shanghai, 200240, China

    JingFang Wang

  3. Shanghai Centre for Bioinformation Technology, Shanghai, 200035, China

    JingFang Wang

Authors
  1. Hui Gu
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  2. HaiFeng Chen
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  3. DongQing Wei
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  4. JingFang Wang
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Correspondence to DongQing Wei or JingFang Wang.

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Gu, H., Chen, H., Wei, D. et al. Molecular dynamics simulations exploring drug resistance in HIV-1 proteases. Chin. Sci. Bull. 55, 2677–2683 (2010). https://doi.org/10.1007/s11434-010-3257-6

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  • DOI: https://doi.org/10.1007/s11434-010-3257-6

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