This project focuses on the study of membranes and carbohydrates by molecular dynamics computer simulation. Modeling studies, primarily on proteins and in collaboration with experimental groups, are also carried out.? ? This years accomplishments primarily concerned force field and method development, and NMR relaxation studies.? ? Force fields (FF) on three classes of compounds, ethers, carbohydrates, and lipids, were developed. All involved extensive ab initio calculations on small model compounds, followed by extensive molecular dynamics simulations on the target systems to ensure that a variety of target data were reproduced. The first CHARMM ether FF was published (4), and follow-up work on polyethylene glycol will be submitted shortly. Following validation of methods on a model carbohydrate, 2- Ethoxy Tetrahydropyran (3), a comprehensive reparameterization of the CHARMM carbohydrate FF was carried out for monosaccharides. Excellent agreement with experimental pucker angles, and the distributions and relaxation rates of the exocyclic torsion hydroxyl group, and solution density data has been obtained. Lastly, the reparameterization of the lipid FF is nearly complete. The key turned out to be a hydrogen bond between the carbonyl group of chain 2 and the glycerol group. This previously unknown interaction leads the splitting of the deuterium order parameters for the carbon 1 of the glycerol and carbon 2 of chain two. A summary of lipid parameterization efforts is contained in (5).? ? 31C and 31P spin lattice relaxation rates were evaluated for two different sized DPPC bilayers and compared with experiment. Agreement is excellent, and demonstrated that collective motions are not playing a substantial role in NMR relaxation over the frequency range 0.022 to 21.1 T. Fits to an analytic model then demonstrated that the primary component of the slow relaxation time observer in the NMR arises from lipid wobble. These results substantially increase confidence in current FF, and lend fundamental insight into the underlying dynamics of membranes.
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