POSITIONING HYDROGEN-ATOMS BY OPTIMIZING HYDROGEN-BOND NETWORKS IN PROTEIN STRUCTURES

A method is presented that positions polar hydrogen atoms in protein s tructures by optimizing the total hydrogen bond energy. For this goal, an empirical hydrogen bond force field was derived from small molecul e crystal structures. Bifurcated hydrogen bonds are taken into account . The procedure also predicts ionization states of His, Asp, and Glu r esidues, During optimization, sidechain conformations of His, Gin, and Asn residues are allowed to change their last chi angle by 180 degree s to compensate for crystallographic misassignments. Crystal structure symmetry is taken into account where appropriate. The results can hav e significant implications for molecular dynamics simulations, protein engineering, and docking studies, The largest impact, however, is in protein structure verification: over 85% of protein structures tested can be improved by using our procedure. (C) 1996 Wiley-Liss, Inc.