Empirical Hydrogen‐Bond Potential Functions—An Old Hat Reconditioned

Abstract

The accurate description of hydrogen-bond interactions is of vital importance for the computational modeling of biological systems. Standard force field (FF) as well as semiempirical quantum mechanical (SQM) methods are now known to have considerable problems with the accurate description of hydrogen bonds. It was found that the performance of SQM methods can be greatly improved with empirical hydrogen-bond correction terms. In the first part of this work we review the improvements developed during the recent revival of dedicated hydrogen-bond terms, also in the light of earlier FF-related work. The second part presents new findings connected to open questions in this field, namely, a study on the importance of angular and torsional information, a scheme how to avoid atom-type-defined target angles and a reduced version of our DH(+) model for the application to force-field methods and physically motivated protein-ligand scoring functions. Our results highlight the importance of using a complete geometric description (including angular and torsional coordinates) for the accurate treatment of hydrogen bonding. The reduced DH(+) model-applied to a modified version of the UFF force field-shows a much improved accuracy for non-covalent interactions also with FF methods, with gains in accuracy by more than one order of magnitude.