Toward a Practical Method for Adaptive QM/MM Simulations

Abstract

We present an accurate adaptive multiscale molecular dynamics method that will enable the detailed study of large molecular systems that mimic experiment. The method treats the reactive regions at the quantum mechanical level and the inactive environment regions at lower levels of accuracy, while at the same time molecules are allowed to flow across the border between active and environment regions. Among many other things, this scheme affords accurate investigation of chemical reactions in solution. A scheme like this ideally fulfills the key criteria applicable to all molecular dynamics simulations: energy conservation and computational efficiency. Approaches that fulfill both criteria can, however, result in complicated potential energy surfaces, creating rapid energy changes when the border between regions is crossed. With the difference-based adaptive solvation potential, a simple approach is introduced that meets the above requirements and reduces fast fluctuations in the potential to a minimum. In cases where none of the current adaptive QM/MM potentials are able to properly describe the system under investigation, we use a continuous force scheme instead, which, while no longer energy conserving, still retains a related conserved quantity along the trajectory. We show that this scheme does not introduce a significant temperature drift on time scales feasible for QM/MM simulations.

Toward Hamiltonian Adaptive QM/MM: Accurate Solvent Structures Using Many-Body Potentials

“…Adaptive resolution methods address this issue by dynamically assigning molecules HR or LR character based on their proximity to the active site. [6][7][8][9][10][11][12][13] Generally, this procedure involves a transition region that connects smoothly the active and environment regions (T-region, Figure 1). The solvent molecules in the T-region have partial HR and partial LR character, and the description of each solvent molecule s smoothly changes from HR to LR (or vice versa) as it moves across the region.…”

“…(DD: among the other problems that we do not consider here, we could also mention that the number of electrons may not be conserved and that we remove electronic degrees of freedom) Hamiltonian formalism (energy conserving). 6,8 In all practical situations, the proposed methods failed to provide reliable solvent structures, while alternative non-Hamiltonian schemes 3 performed much better in this respect. 8,18 Similar findings also directed MM/CG developments 19 , until very recently, when a Hamiltonian approach was introduced (H-AdResS) that conserves both energy and solvent structure.…”

“…The novel approach is an extension of current adaptive QM/MM formulations, and is very general in that it can be combined with many of the available flavors. 6,8,9 This paper is organized as follows. In Section 2 we introduce the theory behind adaptive dual-resolution simulations.…”

“…We then rewrite the adaptive QM/MM (many-body) expressions so that we can define the criteria for a 'per particle' correction analogue to MM/CG. Finally, we discuss a simple correction that has been applied in previous works, 7,8,22 and introduce our novel HadQMMM correction.…”

PyADF — A scripting framework for multiscale quantum chemistry

“…Other recent and ongoing work in our groups also relies on PyAdf. For instance, the code for performing adaptive QM/MM molecular dynamics simulations developed by Bulo et al 67,68 uses PyAdf for executing the QM calculations.…”