Highly accurate computational characterization of weak interactions in biologically relevant prototypes: From hydrogen bonding in the water trimer to pi stacking in protein/ligand binding

Weak intermolecular forces are extremely important in a broad spectrum of chemical and biological applications. Weakly bound systems are particularly interesting to study because of their extremely small binding energies that demand the use of high accuracy electronic structure calculations. Section I introduces the tools of a quantum chemist, including methods and basis sets. A short review of the importance of weakly-bound biological molecules is provided in Section II. The following research details studies on weakly bound systems. Section III reports a highly accurate characterization of six low-lying stationary points on the cyclic water trimer potential energy surface. This research provides valuable energetic data, which hopefully will improve theoretical descriptions of water. Section IV examines the use of density functional theory (DFT) for characterizing a simple hydrogen-bonded system, water dimer. In Section V QM:QM methods and DFT are evaluated for use in solvation of amino acids. This research on hydrogen-bonded interactions with water has yielded accurate energies, characterizations of stationary points, and systematic evaluations of methods.;One weak interaction especially prevalent in biological systems is the pi stacking interaction. Currently, benzene dimer is the most studied and most popular model of pi stacking interactions. However, this homogeneous dimer is not representative of many biological systems that participate in pi stacking because heteroatoms are present in many biological aromatic rings. In Section VI the cyanogen/diacetylene, triazine/benzene, and triazine/triazine dimers have been used to more closely model the interaction between adenine-bearing ligands and aromatic amino acid side chains. These prototypes reveal the energetic differences that heteroatoms introduce in pi stacking interactions. The methods developed in Section VI are then applied to study phenylalanine/adenine in Section VII. This study determines the magnitude of the pi stacking interaction in Phe/adenine compared to benzene/benzene predictions. The overall results from research presented in Sections III--VII are summarized in Section VIII. This research presents a significant contribution to the understanding of an assortment of weak interactions.