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

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

The European Physical Journal E

Springer

Lugar: Paris; Año: 2015

We carry out a time-averaged contact matrix study to reveal the existence of protein backbone hydrogen bonds (BHBs) whose net persistence in time diers markedly form their corresponding PDB-reported 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 nd a signicant 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.