(513fx) Multiscale Modeling of Chemical Reactions: From Physics-Based Reactive Force Fields to Mixed-Resolution Reactive Coarse-Grained Models

Current quantum mechanical methods used for modeling chemical reactions, such as the density functional theory (DFT) and the coupled-cluster theory, are too expensive to sample the configurational space ergodically in systems containing >50-100 atoms, commonly encountered in biochemistry and liquid-phase catalysis. Therefore, there is an urgent need to develop approximate, more computationally efficient approaches that would pave the way to simulating more experimentally relevant larger length and longer time scales. To this end, we propose two methods that hold promise to make reaction barrier predictions in larger systems more affordable at the minimal accuracy loss.

First, we introduce the simple, parameter-free reactive potential [1], obtained by systematic approximation of Kohn-Sham DFT equations at the independent atom limit using the classic Adams-Gilbert-Weeks-Anderson theory of localized orbitals [2]. Remarkably, we find the method to be more accurate than the commonly employed semiempirical reactive force fields, at least for model molecules considered.

Second, we describe the density functional theory-based quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM) methodology [3], aimed at reducing the cost of QM/MM calculations by coarse-graining the MM part in systems with complex MM dynamics. We find that for the model reaction in a non-polar solvent, the difference in QM/CG-MM vs. QM/MM reaction barriers is only ~1.5 kcal/mol, which is less than the typical DFT errors.

Finally, we discuss the generalization of the proposed approaches to more general chemistries and potential challenges ahead.

References:

1. Mironenko, A. V.; Voth, G. A. Nonempirical Reactive Potential Derived from Asymptotic Density Functional Theory. Under Review.
2. Weeks, D.; Anderson, P.W.; and Davidson, A. G. H. Non-Hermitian Representations in Localized Orbital Theories. J. Chem. Phys. 58, 1388 (1973)
3. Mironenko, A. V.; Voth, G. A. Density Functional Theory-Based Quantum Mechanics/Coarse-Grained Molecular Mechanics: Theory and Implementation. Submitted.