?Chameleonic? backbone hydrogen bonds in protein binding and as drug targets

C.A. MENÉNDEZ; S. ACCORDINO; D. C. GERBINO; G. A. APPIGNANESI

European Physical Journal e

EDP Sciences - Springer Verlag - Societa Italiana di Fisica

Lugar: Bologna; Año: 2015 vol. 38 p. 107 - 112

1292-8941

We carry out a time-averaged contact matrix study to reveal the existence of protein backbone hydrogen bonds (BHBs) whose net persistence in time differs markedly form their corresponding PDBreported state. We term such interactions as ?chameleonic? BHBs, CBHBs, precisely to account for their tendency to change the structural prescription of the PDB for the opposite bonding propensity in solution. We also find a significant enrichment of protein binding sites in CBHBs, relate them to local water exposure and analyze their behavior as ligand/drug targets. Thus, the dynamic analysis of hydrogen bond propensity might lay the foundations for new tools of interest in protein binding-site prediction and in lead optimization for drug design.