AbstractsA discussion of Hartree damping in closed-shell Hartree-Fock theory is given indicating when the method might force convergence of intrinsic3lly divergent cases. An alternative, but closely related principle, "level shifting" is described, and the advantages of the latter procedure discussed.O n prksente une discussion de l'amortissement de Hartree dans la thtorie de HartreeFock pour des couches complttes en indiquant quand cette mkthode-ci peut imposer la convergence dans les cas divergents intrinstques. Un prockdk alternatif mais rapprocht, "le dkplacement des niveaux" est dkcrit et ses avantages sont discutbs.Die Hartree-Dampfung in der Hartree-Fock-Theor& fur abgeschlossene Schalen wird diskutiert. Es wird angegeben, wenn mit dieser Methode Konvergenz in wesentlich divergenten Fallen gezwungen werden kann. Ein alternatives aber nahe verwandtes Verfahren, "Niveauverschiebung," wird beschrieben, und die Vorteile dieses letzten Verfahrens werden diskutiert.

Semi-empirical calculations including an empirical dispersive correction are used to calculate intermolecular interaction energies and structures for a large database containing 156 biologically relevant molecules (hydrogen-bonded DNA base pairs, interstrand base pairs, stacked base pairs and amino acid base pairs) for which MP2 and CCSD(T) complete basis set (CBS) limit estimates of the interaction energies are available. The dispersion corrected semi-empirical methods are parameterised against a small training set of 22 complexes having a range of biologically important non-covalent interactions. For the full molecule set (156 complexes), compared to the high-level ab initio database, the mean unsigned errors of the interaction energies at the corrected semi-empirical level are 1.1 (AM1-D) and 1.2 (PM3-D) kcal mol(-1), being a significant improvement over existing AM1 and PM3 methods (8.6 and 8.2 kcal mol(-1)). Importantly, the new semi-empirical methods are capable of describing the diverse range of biological interactions, most notably stacking interactions, which are poorly described by both current AM1 and PM3 methods and by many DFT functionals. The new methods require no more computer time than existing semi-empirical methods and therefore represent an important advance in the study of important biological interactions.

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Crystallographic and computational methods have been used to study the binding of two monosaccharides (glucoside and mannoside) to concanavalin-A. The 2 structure of glucoside bound concanavalin-A is reported and compared with the 2 Ó Ó structure of the mannoside complex. The interaction energies of the substrate in each crystallographic subunit were calculated by molecular mechanics and found to be essentially the same for both sugars. Further energy minimisation of the active site region of the subunits did not alter this conclusion. Information from crystallographic B-factors was interpreted in terms of mobility of the sugars in the combining site. Molecular dynamics (MD) was employed to investigate mobility of the ligands at the binding sites. Switching between di †erent binding states was observed for mannoside over the ensemble in line with the crystallographic B-factors. A calculated average interaction energy was found to be more favourable for mannoside than glucoside, by 4.9 ^3.6 kcal mol~1 (comparable with the experimentally determined binding energy di †erence of 1.6 ^0.3 kcal mol~1). However, on consideration of all terms contributing to the binding enthalpy a di †erence is not found. This work demonstrates the difficulty in relating structure to thermodynamic properties, but suggests that dynamic models are needed to provide a more complete picture of ligandÈreceptor interactions.