An efficient Monte Carlo method for calculating <i>ab initio</i> transition state theory reaction rates in solution

Iftimie, Radu; Salahub, Dennis R.; Schofield, Jeremy

doi:10.1063/1.1622653

Cited by 19 publications

(21 citation statements)

References 46 publications

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“…It should be mentioned that alternative methods to perform QM/MM FEPs have been suggested, e.g. using a linear-response approximation [30] or MM-guided enhanced sampling [24,26,87,88,89,90,91]. However, such approaches require simulations or extensive sampling at the QM/MM level.…”

Section: Discussionmentioning

confidence: 99%

Convergence of QM/MM free-energy perturbations based on molecular-mechanics or semiempirical simulations

Heimdal

Ryde

2012

Phys. Chem. Chem. Phys.

103

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Lately, there has been great interest in performing free-energy perturbation (FEP) at the combined quantum mechanics and molecular mechanics (QM/MM) level, e.g. for enzyme reactions. Such calculations require extensive sampling of phase space, which typically is prohibitive with density-functional theory or ab initio methods. Therefore, such calculations have mostly been performed with semiempirical QM (SQM) methods, or by using a thermodynamic cycle involving sampling at the MM level and perturbations between the MM and QM/MM levels of theory. However, the latter perturbations typically have convergence problems, unless the QM system is kept fixed during the simulations, because the MM and QM/MM descriptions of the internal degrees of freedom inside the QM system are too dissimilar. We have studied whether the convergence of the MM -QM/MM perturbation can be improved by using a thoroughly parameterised force field or by using SQM/MM methods. As a test case we use the first half-reaction of haloalkane dehalogenase and the QM calculations are performed with the PBE, B3LYP, and TPSSH density-functional methods. We show that the convergence can be improved with a tailored force field, but only locally around the parameterised state. Simulations based on SQM/MM methods using the MNDO, AM1, PM3, RM1, PDDG-MNDO, and PDDG-PM3 Hamiltonians have slightly better convergence properties, but very long simulations are still needed (B10 ns) and convergence is obtained only if electrostatic interactions between the QM system and the surroundings are ignored. This casts some doubts on the common practice to base QM/MM FEPs on semiempirical simulations without any reweighting of the trajectories.

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Section: Discussionmentioning

confidence: 99%

Convergence of QM/MM free-energy perturbations based on molecular-mechanics or semiempirical simulations

Heimdal

Ryde

2012

Phys. Chem. Chem. Phys.

103

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“…40 Many methods are developed to overcome this problem. [41][42][43][44][45][46][47][48][49][50][51] To overcome the drawback of the previous method, we introduced a new efficient sampling scheme to obtain average physical properties. We combined this new scheme with a multireference perturbation theory that we developed.…”

Section: Introductionmentioning

confidence: 99%

Solvent effect on the absorption spectra of coumarin 120 in water: A combined quantum mechanical and molecular mechanical study

Sakata

Kawashima

Nakano

2011

The Journal of Chemical Physics

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The solvent effect on the absorption spectra of coumarin 120 (C120) in water was studied utilizing the combined quantum mechanical∕molecular mechanical (QM∕MM) method. In molecular dynamics (MD) simulation, a new sampling scheme was introduced to provide enough samples for both solute and solvent molecules to obtain the average physical properties of the molecules in solution. We sampled the structure of the solute and solvent molecules separately. First, we executed a QM∕MM MD simulation, where we sampled the solute molecule in solution. Next, we chose random solute structures from this simulation and performed classical MD simulation for each chosen solute structure with its geometry fixed. This new scheme allowed us to sample the solute molecule quantum mechanically and sample many solvent structures classically. Excitation energy calculations using the selected samples were carried out by the generalized multiconfigurational perturbation theory. We succeeded in constructing the absorption spectra and realizing the red shift of the absorption spectra found in polar solvents. To understand the motion of C120 in water, we carried out principal component analysis and found that the motion of the methyl group made the largest contribution and the motion of the amino group the second largest. The solvent effect on the absorption spectrum was studied by decomposing it in two components: the effect from the distortion of the solute molecule and the field effect from the solvent molecules. The solvent effect from the solvent molecules shows large contribution to the solvent shift of the peak of the absorption spectrum, while the solvent effect from the solute molecule shows no contribution. The solvent effect from the solute molecule mainly contributes to the broadening of the absorption spectrum. In the solvent effect, the variation in C-C bond length has the largest contribution on the absorption spectrum from the solute molecule. For the solvent effect on the absorption spectrum from the solvent molecules, the solvent structure around the amino group of C120 plays the key role.

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“…This is a particularly challenging problem when one is dealing with ab initio QM systems in QM(ai)/MM simulations. Addressing the need for properly sampling ab initio surfaces has, however, led to several important advances, 45,46,[88][89][90][91][92][93][94][95] many of which 45,46,90,91,[93][94][95] exploit our idea 46,96 of utilizing a classical potential as a reference for QM/MM calculations. Now similarly to the cycle shown in Fig.…”

Section: Iv5 Qm/mm and Related Strategiesmentioning

confidence: 99%

Multiscale modeling of biological functions

Kamerlin

Warshel

2011

Phys. Chem. Chem. Phys.

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Recent years have witnessed a tremendous explosion in computational power, which in turn has resulted in great progress in the complexity of the biological and chemical problems that can be addressed by means of all-atom simulations. Despite this, however, our computational time is not infinite, and in fact many of the key problems of the field were resolved long before the existence of the current levels of computational power. This review will start by presenting a brief historical overview of the use of multiscale simulations in biology, and then present some key developments in the field, highlighting several cases where the use of a physically sound simplification is clearly superior to a brute-force approach. Finally, some potential future directions will be discussed.

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An efficient Monte Carlo method for calculating ab initio transition state theory reaction rates in solution

Cited by 19 publications

References 46 publications

Convergence of QM/MM free-energy perturbations based on molecular-mechanics or semiempirical simulations

Convergence of QM/MM free-energy perturbations based on molecular-mechanics or semiempirical simulations

Solvent effect on the absorption spectra of coumarin 120 in water: A combined quantum mechanical and molecular mechanical study

Multiscale modeling of biological functions

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