Book of Abstracts: Albany 2007
June 19-23 2007
Modelling carbohydrate structure and dynamics
For proteins and nucleic acids, molecular mechanical force fields using fixed atom-centred partial charges have been the mainstay of biomolecular modelling. In the case of carbohydrates, however, describing correct physical behaviour which is influenced by stereoelectronic subtleties (anomeric, exo-anomeric and gauche effects), has proved more challenging at the molecular mechanical level. Here, we describe our efforts to accurately model saccharides via a focused semi-empirical quantum mechanical approach within the framework of the PM3 model. The PM3 Hamiltonian is reparametrized using a genetic algorithm and a training set of molecules. We will discuss the effect of training set size and composition on the quality of the model derived. We will also highlight considerations in obtaining appropriate oligosaccharide benchmarks obtained from high level (correlated) ab initoi quantum mechanical calculations. Prospects of the strategy for accurate modeling of carbohydrates and their conformational behaviour in a condensed phase environment will be outlined.
Richard A. Bryce
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Oxford Road, Manchester, M13 9PL, UK