Quantum chemical investigation of hydrogen-bond strengths and partition into donor and acceptor contributions

We present a simple increment model for use in the rapid scoring of hydrogen bond strengths employing 15 chemically diverse donor and 28 acceptor terms. The increments cover a large variety of hydrogen bond donor and acceptor groups and are more specific than SYBYL atom types. The increments have been fitted to quantum chemical ab initio interaction energies of 81 small hydrogen‐bonded complexes determined at the level of second‐order Møller‐Plesset perturbation theory (MP2). The complexes have been chosen such as to represent the most important types of donor‐acceptor pairs found in biological systems. Sulphur is found to be a strong hydrogen bond acceptor while its donor capacities are weak. By taking CH acidic H donors into account, a linear correlation between MP2 energies and the increment model with a coefficient of correlation of r² = 0.994 has been accomplished. The transferability of the fitted parameters has been assessed on a second set of complexes including larger molecules of biological relevance. Very good agreement has been achieved for noncyclic hydrogen bonds. Cooperative effects are not accounted for by the current increment model. For this reason, binding energies of strong cyclic hydrogen bonds, as e.g. present in DNA base pairs, are underestimated by about 30–40%. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007