Acta Phys. -Chim. Sin. ›› 2005, Vol. 21 ›› Issue (11): 1229-1234.doi: 10.3866/PKU.WHXB20051107

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Study on Interaction between HIV-1 Integrase and Its Dicaffeoyl Inhibitors through Molecular Modeling Approach

LIU Chun-li; LI Chun-hua; CHEN Wei-zu; WANG Cun-xin   

  1. College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100022
  • Received:2005-04-04 Revised:2005-05-23 Published:2005-11-15
  • Contact: WANG Cun-xin

Abstract: The binding mode of a series of dicaffeoyl or digalloyl pyrrolidine and furan derivatives inhibitors with HIV-1 integrase was proposed by using molecular docking and molecular dynamics (MD) simulation methods. The results indicate that the interactions between HIV-1 integrase conserved DDE motif and caffeoyl or galloyl group of inhibitors play a critical role in the inhibition of integrase activity, and the binding affinity between integrase and inhibitors was improved when the side chain groups were galloyls. The linear interaction energy (LIE) method was used to calculate the binding free energies of HIV-1 integrase and their inhibitors, the predicted values are in good agreement with the experimental data, with a root-mean-square deviation (RMSD) of 1.39 kJ•mol-1. The above results provide useful information for structure-based HIV-1 integrase inhibitor design.

Key words: HIV-1 integrase inhibitor, Integrase, Molecular dynamics simulation, Dicaffeoyl group, Digalloyl group