Energetics of protein backbone hydrogen bonds and their local electrostatic environment

MD simulation study of several peptides including a polyalanine, a helix (pdb:2I9M), and a leucine zipper were carried out to investigate hydrogen bond energetics using dynamic polarized protein-specific charge (DPPC) to account for the polarization effect in protein dynamics. Results show that the backbone hydrogen-bond strength is generally correlated with its specific local electrostatic environment, measured by the number of water molecules near the hydrogen bond in the first solvation shell. The correlation coefficient is found to be 0.89, 0.78, and 0.80, respectively, for polyalanine, 2I9M protein, and leucine zipper. In the polyalanine, the energies of the backbone hydrogen bonds are very similar to each other due to their similar local electrostatic environment. The current study helps demonstrate and support the understanding that hydrogen bonds are stronger in a hydrophobic surrounding than in a hydrophilic one. For comparison, the result from simulation using standard force field shows a much weaker correlation between hydrogen bond energy and local electrostatic environment due to the lack of polarization effect in the force field.