Computational investigation of the HIV‐1 Rev multimerization using molecular dynamics simulations and binding free energy calculations

• DOI: 10.1002/prot.24057
• Publication Date: 2012-02-20T07:36:38Z
• Authors: Tom Venken; Dirk Daelemans; Marc De Maeyer; Arnout Voet
• Keywords: Tetramer; Conformational entropy

Abstract The HIV Rev protein mediates the nuclear export of viral mRNA, and is thereby essential for production late proteins in replication cycle. forms a large organized multimeric protein‐protein complex proper functioning. Recently, three‐dimensional structures dimer tetramer have been resolved provide basis thorough structural analysis binding interaction. Here, molecular dynamics (MD) free energy calculations were performed to elucidate forces thriving dimerization higher order multimerization protein. It found that despite differences between each crystal structure, both display similar behavior according our calculations. Our based on mechanics‐generalized Born surface area (MM/GBSA) configurational entropy approach demonstrates site much weaker than site. In addition, quantitative hot spot combined with mutational reveals most contributing amino acid residues interactions agreement experimental results. Additional interface, which are important investigation thermodynamics here could be further step development novel antiretrovirals using structure drug design. Moreover, variability angle monomer as measured during MD simulations suggests role allowing flexibility arginine rich domain (ARM) accommodate RNA binding. Proteins 2012; © 2012 Wiley Periodicals, Inc.