Binding of N-substituted pyrrole derivatives to HIV-1 gp41

作者：Song, Kunzhong^*; Bao, Ju; Sun, Yueming; Zhang, John Z H

来源：Journal of Theoretical and Computational Chemistry, 2014, 13(2): 1450018.

DOI：10.1142/S0219633614500187

• HIV-1 entry fusion
• binding modes
• gp41
• binding free energy
• carboxy group

Developing small molecule inhibitors of human immunodeficiency virus type 1 (HIV-1) fusion has attracted significant interest. Recently, Jiang have reported several natural and synthetic N-substituted pyrrole derivatives targeting gp41 that are experimentally shown to inhibit cell-cell fusion in the low micromolar range. In order to help gain insight on the binding mechanism, we carried out computational study to help identify possible binding modes and to characterize structures of binding complexes. Detailed gp41-molecule binding interactions and free energies of binding are obtained through molecular dynamics (MD) simulation and MM-PBSA calculation. Specific molecular interactions in the gp41-inhibitor complexes are identified. Current computational study complements the corresponding experimental investigation and provides theoretical understanding on the binding mechanism which is helpful for further refinement of small molecule inhibitors of gp41.

• 出版日期2014-3
• 单位东南大学; 华东师范大学