Article Bioinformatics

Chinese Science Bulletin

, Volume 55, Issue 24, pp 2677-2683

First online:

Molecular dynamics simulations exploring drug resistance in HIV-1 proteases

  • Hui GuAffiliated withCollege of Life Sciences and Biotechnology, Shanghai Jiaotong University
  • , HaiFeng ChenAffiliated withCollege of Life Sciences and Biotechnology, Shanghai Jiaotong University
  • , DongQing WeiAffiliated withCollege of Life Sciences and Biotechnology, Shanghai Jiaotong University Email author 
  • , JingFang WangAffiliated withShanghai Centre for Systems Biomedicine, Shanghai Jiaotong UniversityShanghai Centre for Bioinformation Technology Email author 

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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.


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