MS12-P07 Conservation and Variability in Hydrogen Bonding in Proteins Matthew Merski (Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Warsaw, Poland) Jakub Skrzeczkowski (Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Warsaw, Poland) Maria W. Górna (Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Warsaw, Poland)email: merski@gmail.com
Hydrogen bonds are an essential part of the structure and function of proteins, defining the secondary structure and the overall fold of the protein as well as being important components of the active sites of enzymes. However, despite the widespread belief that proteins are evolved to sustain a single, folded structure, there is significant, empirically demonstrable variability in the hydrogen bonding pattern of proteins, even within sets of identical protein structures in which there is little overall structural variation. Hydrogen bond variability has been recently clearly demonstrated in a set of structures of a single protein bound to a homologous series of ligands[1]. However, neither the extent of this variability, nor its function has been widely otherwise remarked upon in the current literature. We catalogue the variability of hydrogen bonding patterns in all currently publically known protein structures present in the Protein Data Bank[2]. We use a geometric definition of hydrogen bonding in proteins to focus on the kind of data available from x-ray structures of proteins. We compared the hydrogen bonding pattern between all instances of identical or nearly identical proteins (≥ 90 % sequence identity) which have been deposited at least 10 times in the PDB (n ~ 6500) and used this redundancy to measure the inherent variability in a given hydrogen bond. This geometric definition will allow treatment of both strong (e.g. OH-O, NH-O) and weak/non-traditional (e.g. CH-O, NH-π, OH/NH-S, etc.) protein hydrogen bonds. Identification and characterization of this variability will help to understand the role of this variability in protein structure and also aid in future protein engineering and design efforts.
References:

[1] Merski M., Fischer M., Balius T.E., Eidam O., Shoichet B.K. (2015) Proc Natl Acad Sci U S A, 112(16), 5039-44

[2] Berman H.M., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissig H., Shindyalov I.N., Bourne P.E. (2000) Nucl. Acids Res., 28, 235-242
Keywords: hydrogen bond, protein