DEVELOPMENT AND APPLICATION OF A HIERARCHICAL PROTOCOL FOR AB INITIO PREDICTION

Carnegie-Mellon University, Pittsburgh PA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The interest in current computational biology is shifting from predicting the three-dimensional structure of proteins to simulating and understanding the mechanism of action of more complicated systems such as protein-protein, protein-nucleic acid complexes, and signal transduction processes. Research presented in this proposal is based on extension of our physics-based coarse-grained force-field UNRES. Three main extensions which we propose are: i) improved model for side chain-side chain interactions for better description of charge and polar interactions observed in proteins, which are important in molecular recognition and formation of protein-protein complexes;ii) introduction of the O-poshorylated residues into the UNRES model which will allow us to investigate molecular signaling routes;iii) massive parallelization of the code which will allow us to perform very fast MD simulations on systems composed of up to 1000 amino acids residues. We expect that all proposed changes will make our UNRES force-field more useful in understanding mechanism of action and function of large molecular systems that are important from a biological point of view.