New-generation molecular simulation force fields for biomolecules

Molecular simulation is a powerful tool for examining the dynamic behavior of molecular systems and chemical processes. Unfortunately, the computational requirement inherent in even the most efficient ab initio methods precludes their application to simulations of very large systems in the near future. For these systems, approximate methods that are less computationally demanding are required. An area of active research involves the development of improved physical models that reliably describe molecular interactions with minimal parameters and computational overhead.

Recently, a new model for polarization and charge transfer has been introduced that utilizes the electron density as the basic variable and takes into account many-body effects. The generalized chemical potential equalization (CPE) method is a density-functional based approach for inclusion of many-body polarization effects in molecular simulations. The method incorporates quantum chemical properties such as electronegativity and hardness based on their mathematical definitions founded in density-functional theory, and requires minimal overhead relative to conventional force field methods.

A long term objective of the lab is to develop a new generation force field for molecular simulations of biomolecules that includes many-body effects and can be rigorously combined with higher level ab initio methods to produce hybrid potentials (see our QM/MM methods). The force field will involve modification of standard electrostatic point charge terms to include nuclear terms and smooth electron density distributions. These distributions can adjust (polarize) according to the CPE equations to allow a dynamical description of the charge density as a function of conformation and molecular environment.

Current Projects

HAMMERHEAD RIBOZYME

HIV-1 REVERSE TRANSCRIPTASE

Relevent Publications

"A chemical potential equalization method for molecular simulations", D. York, W. Yang, J. Chem. Phys. 104, 159-172 (1996).