An approximate multipole expansion for molecular interactions

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Thesis (Ph.D.)--Georgetown University, 2010.; Includes bibliographical references.; Text (Electronic thesis) in PDF format. Computer simulations of larger systems and longer timescales are important in understanding biological processes such as protein folding and protein-DNA interactions at a molecular level. As larger macromolecules are studied, accurate and efficient approaches are needed that recast potential energy functions from atomistic models that describe interactions between individual atoms into so-called coarse-grained models that describe interactions between groups of atoms. The biggest stumbling block has been in the electrostatic interactions between the coarse-grained particles. Here, water and representative biomolecules are modeled through our approximate multipole expansion (AME) for the electrostatics. In simulations of liquid water, the soft-sticky dipole-quadrupole-octupole (SSDQO) model for water, which uses AME electrostatics, gave structural, thermodynamic, dynamic and dielectric properties in good agreement with experiment not only at ambient conditions but at a wide range of temperatures and pressures. The results for SSDQO are comparable to the most sophisticated (and very computationally slow) rigid atomistic models but SSDQO is at least two times faster than the fastest atomistic model. In addition, for simulations of biomolecules in aqueous solutions, SSDQO combined with a typical (atomistic) potential energy function for the biomolecule gave good solvation structure for the water. Moreover, SSDQO solvation of biomolecules and simple ions is more consistent with the limited experimental data and results from QM/MM simulations than atomistic water models. Given the good results for water, a generalized coarse-grained model for molecules was developed using AME electrostatics and an orientation-dependent van der Waals interaction, referred to as the soft-sticky approximate multipole expansion (SSAME) model. Simulations of benzene, methanol, and phenol both as pure liquids and in aqueous solution using SSAME were comparable to all-atom simulations but with much greater computational efficiency. Overall, our AME is an important step in developing coarse-grained models for realistic simulations of biological macromolecules in aqueous solution.
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