We explore the possibility of using a fragment-based approach to decomposing a molecular system such that the total energy of the system can be stated as the sum of self energies of individual fragments and the pair interaction energies of all fragments with their neighbors. This framework, amenable to protein design, fragment-based ligand docking, and protein structure prediction, is extended for applicability to condensed-phase simulations with explicit representation of all atoms. Reciprocally, the extension to all-atom systems incorproates aspects of these simulations into docking and design studies, including explicit water molecules and an unprecedented level of receptor flexibility. With explicit control over the approximations being made in order to transition from a full molecular mechanics potential and trajectory sampling protocol to forms more amenable to docking and design studies, the sources of error in free energy estimates of the latter applications can be dissected and addressed.

Scalable, fragment-based ensemble generator for docking studies, structure prediction, and condensed-phase simulations

251st National Meeting (2016)

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