Nature of H-bonding in clusters, liquids, and enzymes: an ab initio, natural bond orbital perspective

Ab initio computational chemistry and Natural Bond Orbital (NBO) analysis provide insight into the electronic principles governing H-bonded clusters. The energetics of such clusters are dominated by cooperative intermolecular delocalization (charge transfer) whose enthalpic and entropic contributions lead to aggregation patterns quite different from those predicted by pairwise-additive empirical potentials in common usage. We outline a Quantum Cluster Equilibrium (QCE) theory that describes gas/liquid thermodynamic properties of H-bonded fluids, and we summarize the general principles of H-bond network formation that appear to govern thermodynamic stability. We compare the H-bond network structures found in simple liquids with that of the ''catalytic triad'' active site of chymotrypsinogen and related serine proteases. A simple ab initio ''gas phase'' cluster model is shown to qualitatively reproduce the H-bond network of the enzyme active site, thereby suggesting its intrinsic electronic and physiological function. We discuss how the non-linearities of H-bond networks can lead to profound increases in structural complexity in the enzyme environment. (C) 1997 Elsevier Science B.V.