Characterization of the Interface of the Bone Marrow Stromal Cell Antigen 2-Vpu Protein Complex via Computational Chemistry
Bone marrow stromal cell antigen 2 (BST-2) inhibits the release of enveloped viruses from the cell surface.Various viral counter measures have been discovered,which allow viruses to escape BST-2 restriction.Human immunodeficiency virus type 1 (HIV-1) encodes viral protein U (Vpu) that interacts with BST-2 through their transmembrane domains and causes the downregulation of cell surface BST-2.In this study,we used a computer modeling method to establish a molecular model to investigate the binding interface of the transmembrane domains of BST-2 and Vpu.The model predicts that the interface is composed of Vpu residues 16,A10,A14,A18,V25,and W22 and BST-2 residues L23,I26,V30,I34,V35,LA1,I42,and T45.Introduction of mutations that have been previously reported to disrupt the Vpu-BST-2 interaction led to a calculated higher binding free energy (MMGBSA),which supports our molecular modeL A pharmacophore was also generated on the basis of this modal.Our results provide a precise modal that predicts the detailed interaction occurring between the transmembrane domains of Vpu and BST-2 and should facilitate the design of anti-HIV agents that are able to disrupt this interaction.
Jinming Zhou Zhixin Zhang Zeyun Mi Xin Wang Quan Zhang Xiaoyu Li Chen Liang Shan Cen
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China Lady Davis Institute for Medical Research and McGill AIDS Centre, Jewish General Hospital, Montreal,
国际会议
南京
英文
77-85
2012-05-13（万方平台首次上网日期，不代表论文的发表时间）