Schrodinger, Inc. proposes to continue developing a novel polarizable force field for proteins and peptides based upon a fluctuating charge (FQ) and dipole model. The force field will include polarizability and solvent effects at a minimal computational cost. Phase I preliminary results show that the FQ model can be fit directly to quantum chemical data for peptides and that the resulting model provides an excellent reproduction of quantum chemical many body energetics of polypeptides. In Phase II, Schrodinger will first use the FQ model to construct a full polarizable force field by constructing a transferable functional form for the electrostatics and then adding van der Waals and valence terms. Secondly, Schrodinger will develop both explicit water and continuum dielectric models of aqueous solvation so that the modeling with the polarizable force field can be carried out in the actual biological environment. The polarizable force field and solvation models will be implemented in a robust molecular modeling code with fast simulation algorithms. Lastly, the force field and simulation algorithms will be rigorously tested to validate that they provide significant improvements over existing fixed charge force fields.
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