Binding of -substituted pyrrole derivatives to HIV-1 gp41.
- Resource Type
- Article
- Authors
- Song, Kunzhong; Bao, Ju; Sun, Yueming; Zhang, John Z. H.
- Source
- Journal of Theoretical & Computational Chemistry. Mar2014, Vol. 13 Issue 2, p-1. 9p.
- Subject
- *SUBSTITUTION reactions
*PYRROLE derivatives
*HIV
*MOLECULAR structure
*MOLECULAR dynamics
*ENZYME inhibitors
*GIBBS' free energy
*CONFORMATIONAL analysis
*COMPUTATIONAL chemistry
*CARBOXYL group
- Language
- ISSN
- 0219-6336
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 -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. Developing orally available small molecule inhibitors of HIV-1 fusion has attracted significant interest over many years. Here several synthetic compounds from Frey's experiment have been calculated to indentify possible binding modes by docking these compounds onto the hydrophobic pocket on gp41 and characterize structures of binding complexes. The gp41-molecule binding Conformations interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Computational result is in general agreement with the corresponding experimental studies and provided helpful information for the binding structure and molecular action with HIV protein at detailed molecule level. The present computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of small molecular gp41 inhibitors. [ABSTRACT FROM AUTHOR]