bound water at protein-protein interfaces partners, roles and hydrophobic bubbles as a conserved motif结合水在蛋白质接口合作伙伴、角色和疏水性泡沫守恒的主题.pdfVIP

Bound Water at Protein-Protein Interfaces: Partners, Roles and Hydrophobic Bubbles as a Conserved Motif 1,3 4,5,6 4,6 4 5,6 Mostafa H. Ahmed , Francesca Spyrakis , Pietro Cozzini , Parijat K. Tripathi , Andrea Mozzarelli , J. Neel Scarsdale2,3, Martin A. Safo1,3, Glen E. Kellogg 1,2,3* 1 Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia, United States of America, 2 Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, Virginia, United States of America, 3 Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, Virginia, United States of America, 4 Department of General and Inorganic Chemistry, University of Parma, Parma, Italy, 5 Department of Biochemistry and Molecular Biology, University of Parma, Parma, Italy, 6 Institute of Biostructures and Biosystems, Rome, Italy Abstract Background: There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region. ˚ Methodology: A data set of 4741 water molecules abstracted from 179 high-resolution (# 2.30 A) X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-