Atomic Detailed Modeling in Structural Genomics and Single Molecule Dynamics

Computer modeling becomes more and more important in structural genomics and protein dynamics study. We have developed computer programs for atomic detailed modeling in protein structure and function prediction. In protein structure prediction, atomic detailed statistical potential has been shown to perform better in near-native structure selection and in structure refinement. In a test set of 65 proteins, the current method can generate near-native structures for 75% of the cases. The statistical potential guided refinement procedure can improve the protein structure for half of the test cases, while keeping the other half unchanged. In structure-based function prediction, we have developed multiresolution statistical potentials and a complex threading algorithm in protein-protein interaction study. In both structure and function prediction, our atomic modeling programs are sufficiently fast for genome scale applications. Finally, an atomic detailed steered molecular dynamics simulation is used in studying protein's mechanical property. Combined with the results from single molecule experiments, we have investigated protein's dynamics-function relationship. The discovery of a hydrogen bond controlled unfolding mechanism has been confirmed by protein engineering and atomic force microscopy experiments.

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