ROLE OF HYDROGEN-BONDS IN PROTEIN-DNA RECOGNITION - A COMPARISON OF GENERALIZED BORN AND FINITE-DIFFERENCE POISSON-BOLTZMANN SOLVATION TREATMENTS

Hydrogen bonds have been accredited with a major role historically, in the formation and stabilization of biomolecular structures. The forma tion of hydrogen bonds at protein-DNA interfaces in aqueous medium inv olves not only favorable interactions of the donor and acceptor functi onal groups but also a loss of interactions between these groups with the solvent water. We have investigated the energetics of about 500 po tential hydrogen bonds occuring at protein-DNA interfaces incorporatin g some recent improvements in biomolecular force fields and solvation treatments. We present here results of our assessment of hydrogen bond contributions to the overall standard free energy of formation of pro tein-DNA complexes obtained with the generalized Born model and finite difference Poisson-Boltzmann methodology for solvation in conjunction with AMBER force field. Our results support the emerging view on the role of electrostatics in general and that of hydrogen bonds in partic ular which is that hydrogen bonds do not drive protein-DNA complex for mation by virtue of the unfavourable cost of the electrostatics of des olvation. They however, act to stabilize the complex once it is formed .