Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
Molecular Motions of Proteins Play Crucial Role in Their Function
Proteins, which are the materials central to cellular function, should not be regarded simply as static pictures as determined by X-ray crystallography. They are dynamic entities in cellular solution with functions governed ultimately by their dynamic character (1). Therefore a complete understanding of the structure-function relationship of a protein requires an analysis of its dynamic behavior and molecular motion.
Using molecular dynamics (MD) simulation or CONCOORD (2) approach, the dynamic behaviors of HIV-1 gp120 envelope glycoprotein and serine protease proteinase K were investigated. Apart from analyses of the conventional structural properties during simulations, the essential dynamics analysis method was used to study the large concerted motions of these two proteins, including the influence of ligand bindings or residue mutations on molecular motions. The results revealed that i) the proteinase K shows relatively rigid internal core with some highly flexible surface loops forming the substrate-binding region, supporting the induce-fit or conformational selection mechanism of substrate binding (3); ii) the removal of Ca2+ cations from proteinase K increases the global conformational flexibility, decreases the local flexibility of substrate-binding region and does not influence the thermal motion of catalytic triad, thus explaining the experimentally determined decreased thermal stability, reduced substrate affinity and almost unchanged catalytic activity upon Ca2+ removal (4); iii) the substrate binding affects the large concerted motions and flexibility behavior of proteinase K suggesting that the variations in substrate-pocket motions can be connected to substrate binding, catalysis and product release (5); amino acid mutations 375 S/W and 423 I/P of HIV-1 gp120 have distinct effects on molecular motions of gp120 (6), facilitating 375 S/W mutant to adopt the CD4-bound conformation while 423 I/P mutant to prefer for CD4-unliganded state (7).
Analyzing the dynamic character of proteins not only is important for the characterization of the functional properties of proteins but also facilitates the reasonable interpretation of experimentally determined structural, biochemical and biological data.
This research was supported by grants from NSFC (No. 30860011) and Yunnan province (2007PY-22), and foundation for Key Teacher of Yunnan University.
1 Laboratory for Conservation and Utilization of Bio-Resources & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming 650091, P. R. China