Computer Modeling and Other Theoretical Studies of Biopo

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Summary: A variety of high level experimental (one and two dimensional NMR) and theoretical (Langevin and molecular dynamics, hydrodynamics, and cluster analysis) were applied to a pair of trisaccharides, enabling conclusions that would have been impossible to reach had the methods been used in isolation. These include: an explanation of the flat T1 profiles of clearly anisotropic molecules (match of tumbling times and spectrometer frequency); evaluation of potential energy functions (possible errors in the substate distribution of the syn minima); quantitative error analysis of the NOE derived distances (use of MD and hydrodynamics to evaluate common assumptions); and, most importantly, insight into the relative flexibility of alpha and beta-linkages in oligosaccharides (alpha-linkages confer rigidity to the molecule). Exhaustive characterizations such as these will eventually enable the prediction the conformation of oligosaccharides when they are bound to proteins, and the design of inhibitors of toxins. A report of this research has been submitted for publication to the Journal of The American Chemical Society. Ab initio (i.e., quantum mechanical) calculations were carried out on ethers and a model compound exhibiting a glycosidic linkage, leading to refinements of the CHARMM force field for carbohydrates. A report of this research will be submitted for publication. Computer modeling was also carried out in support of a project involving a modified protein fragment (I-I-C-N-N-P-H-I-I) associated with a dodecylphosphocholine (DPC) micelle. Molecular dynamics simulations of DPC micelles and peptide/micelle complexes suggest that the peptide lies flat on the micelle surface, and showed rapid rearrangement of the lipids to accommodate the bound peptide. A report of this research has been accepted for publication in Biopolymers.