Advanced Potential Energy Surfaces for Molecular Simulation

Abstract

Advanced potential energy surfaces are defined as theoretical models that explicitly include many-body effects that transcend the standard fixed-charge, pairwise-additive paradigm typically used in molecular simulation. However, several factors relating to their software implementation have precluded their widespread use in condensed-phase simulations: the computational cost of the theoretical models, a paucity of approximate models and algorithmic improvements that can ameliorate their cost, underdeveloped interfaces and limited dissemination in computational code bases that are widely used in the computational chemistry community, and software implementations that have not kept pace with modern high-performance computing (HPC) architectures, such as multicore CPUs and modern graphics processing units (GPUs). In this Feature article we review recent progress made in these areas, including well-defined polarization approximations and new multipole electrostatic formulations, novel methods for solving the mutual polarization equations and increasing the MD time step, combining linear scaling electronic structure methods with new QM/MM methods that account for mutual polarization between the two regions, and the greatly improved software deployment of these models and methods onto GPU and CPU hardware platforms. We have now approached an era where multipole-based polarizable force fields can be routinely used to obtain computational results comparable to state-of-the-art density functional theory while reaching sampling statistics that are acceptable when compared to that obtained from simpler fixed partial charge force fields.

Performance of the AMOEBA Water Model in the Vicinity of QM Solutes: A Diagnosis Using Energy Decomposition Analysis

“…Figure S5 in the Supplementary Material and Figure 2 in Ref. 155 for preliminary results), it might exacerbate the so-called "electron-spill" effect, 156 i.e., the QM region is enormously over-polarized so that the electrons are pulled out of the QM region, and energetically it results in vastly overestimated polarization energies (see Figure S6 and the right panel of Figure S5 in the Supplementary Material). This is related to the aforementioned splitting of multipole moments which effectively places point charges of large magnitude (nuclei of MM atoms) near the QM/MM boundary, while the essential deficiency, nonetheless, is the purely empirical treatment of the repulsive vdW interaction (also termed exchange/Pauli/non-electrostatic repulsion), which fails to preclude the over-polarization of QM density by the electrostatic potential of MM.…”

Computational Optimization of Electric Fields for Improving Catalysis of a Designed Kemp Eliminase

“…Using Gromacs 47 , the 25 lowest energy structures were explicitly solvated using a pre-equilibrated water box. We then performed 50 ps equilibration and then 50 ps production runs in the NPT ensemble using the Tinker software package [49][50][51] and the AMOEBA polarizable force field 45,49 to provide a high quality description of electrostatics in the active site and overall scaffold and solvent. The substrate geometry for the transition state The electric field is projected onto each bond and the value reported is given by the mean of the electric field at the two atoms involved 34 .…”

Finding Our Way in the Dark Proteome

“…However, polarizable models come with an increase in computational expense that in turn limits needed sampling. Nonetheless, recent efforts to reduce the computational expense of polarizable models are starting to take hold 141 , and thus will be an important future direction in the simulation of robust IDP structural ensembles.…”