Title: Conservation of water molecules in protein binding interfaces

Authors: Zhenhua Li; Ying He; Longbing Cao; Limsoon Wong; Jinyan Li

Addresses: School of Computer Engineering, Nanyang Technological University, Block NS4-04-33, 50 Nanyang Avenue, 639798 Singapore ' School of Computer Engineering, Nanyang Technological University, Block NS4-04-33, 50 Nanyang Avenue, 639798 Singapore ' Faculty of Engineering and Information Technology, Advanced Analytics Institute, University of Technology Sydney, CC02.01.207 (Level 1, Building 2), Blackfriars Street, Chippendale, Blackfriars Campus, P.O. Box 123 Broadway, NSW 2007, Australia ' School of Computing, National University of Singapore, Level 3, Building COM1, 13 Computing Drive, 117417 Singapore ' Advanced Analytics Institute, University of Technology Sydney, P.O. Box 123, Broadway NSW 2007, Australia

Abstract: The conservation of interfacial water molecules has only been studied in small data sets consisting of interfaces of a specific function. So far, no general conclusions have been drawn from large-scale analysis, due to the challenges of using structural alignment in large data sets. To avoid using structural alignment, we propose a solvated sequence method to analyse water conservation properties in protein interfaces. We first use water information to label the residues, and then align interfacial residues in a fashion similar to normal sequence alignment. Our results show that, for a water-contacting interfacial residue, substituting it into hydrophobic residues tends to desolvate the local area. Surprisingly, residues with short side chains also tend not to lose their contacting water, emphasising the role of water in shaping binding sites. Deeply buried water molecules are found more conserved in terms of their contacts with interfacial residues.

Keywords: protein-protein interfaces; PPIs; water; substitution; water conservation properties; molecule burial level; interfacial water molecules; bioinformatics; protein binding interfaces; sequence alignment; hydrophobic residues; interfacial residues.

DOI: 10.1504/IJBRA.2012.048968

International Journal of Bioinformatics Research and Applications, 2012 Vol.8 No.3/4, pp.228 - 244

Published online: 05 Dec 2014 *

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