Improving Efficiency in SMD Simulations Through a Hybrid Differential Relaxation Algorithm

Ramírez, Claudia Lilián; Zeida, Ari; Jara, Gabriel E.; Roitberg, Adrián E.; Martí, Marcelo A.

doi:10.1021/ct500672d

Cited by 19 publications

(27 citation statements)

References 43 publications

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“…This is similar to the microiterative approach, 60 sequential sampling, 15 , and hybrid differential relaxation algorithm. 61 If the QM/MM sampling frequency remains at 100 timesteps, then during each interval there will be 100 frames with identical solute geometry where MESS-E-QM/MM can be applied to reliably estimate QM/MM energies. Since the HOMO-LUMO gap is expected to be insensitive to molecular geometry, we expect the same scaling factor for MESS-E can be applied for all solute geometries.…”

Section: Discussionmentioning

confidence: 99%

Computation of Hydration Free Energies Using the Multiple Environment Single System Quantum Mechanical/Molecular Mechanical Method

König¹,

Pickard

et al. 2015

J. Chem. Theory Comput.

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A recently-developed MESS-E-QM/MM method (multiple-environment single-system quantum mechanical molecular/mechanical calculations with a Roothaan-step extrapolation) is applied to the computation of hydration free energies for the blind SAMPL4 test set and for twelve small molecules. First, free energy simulations are performed with classical molecular mechanics force field using fixed-geometry solute molecules and explicit TIP3P solvent, then the non-Boltzmann-Bennett method is employed to compute the QM/MM correction (QM/MM-NBB) to the molecular mechanical hydration free energies. For the SAMPL4 set, MESS-E-QM/MM-NBB corrections to the hydration free energy can be obtained 2 or 3 orders of magnitude faster than fully converged QM/MM-NBB corrections, and, on average, the hydration free energies predicted with MESS-E-QM/MM-NBB fall within 0.10–0.20 kcal/mol of full-converged QM/MM-NBB results. Out of five density functionals (BLYP, B3LYP, PBE0, M06-2X, and ωB97X-D), the BLYP functional is found to be most compatible with the TIP3P solvent model and yields the most accurate hydration free energies against experimental values for solute molecules included in this study.

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Section: Discussionmentioning

confidence: 99%

Computation of Hydration Free Energies Using the Multiple Environment Single System Quantum Mechanical/Molecular Mechanical Method

König¹,

Pickard

et al. 2015

J. Chem. Theory Comput.

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“…(Ramírez, Zeida, Jara, Roitberg, & Martí, 2014). This scheme allows faster equilibration of the classical environment during the steering process that drives the QM system along the reaction under study.…”

Section: Hybrid Differential Relaxation Algorithmmentioning

confidence: 99%

“…Recently, we have shown (Ramírez et al, 2014) that it is possible to obtain an accurate FEP in significant less computational time, when using JR with the HyDRA scheme. This provides an invaluable tool for QM/MM studies of enzymatic reactions especially those requiring significant protein reorganization along the chemical step.…”

Section: Theoretical Basis Of Hydramentioning

confidence: 99%

“…This is possible since external force and thus work are only computed during the joint (QM/MM) step. In other words, HyDRA takes advantage of the fact that in the context of MSMD-JR, only the force on the reaction coordinate contributes to the free energy and the environment can relax freely at no cost, when it remains frozen (Ramírez et al, 2014).…”

Section: Theoretical Basis Of Hydramentioning

confidence: 99%

“…Although a detailed study of the 10-100 times reduction in computational cost was presented in our previous work (Ramírez, Zeida, Jara, Roitberg, & Martí, 2014), it is interesting to analyze the performance of the HyDRA method in the context of similar works on previously mentioned enzymes. Despite being difficult to make a detailed comparison when different codes, levels of theory, and systems were employed, the total number of QM/MM steps required to obtain the profile can be used as a code-system-independent parameter.…”

Section: Final Remark On Qm/mm Studies Of Enzyme Reaction Mechanismsmentioning

confidence: 99%

See 2 more Smart Citations

Efficient Calculation of Enzyme Reaction Free Energy Profiles Using a Hybrid Differential Relaxation Algorithm

Romero¹,

Martin²,

Ramírez³

et al. 2015

Combined Quantum Mechanical and Molecular Mechanical Modelling of Biomolecular Interactions

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On the accurate estimation of free energies using the jarzynski equality

et al. 2018

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The Jarzynski equality is one of the most widely celebrated and scrutinized nonequilibrium work theorems, relating free energy to the external work performed in nonequilibrium transitions. In practice, the required ensemble average of the Boltzmann weights of infinite nonequilibrium transitions is estimated as a finite sample average, resulting in the so‐called Jarzynski estimator, normalΔFfalse^J. Alternatively, the second‐order approximation of the Jarzynski equality, though seldom invoked, is exact for Gaussian distributions and gives rise to the Fluctuation‐Dissipation estimator normalΔFfalse^FD. Here we derive the parametric maximum‐likelihood estimator (MLE) of the free energy normalΔFfalse^ML considering unidirectional work distributions belonging to Gaussian or Gamma families, and compare this estimator to normalΔFfalse^J. We further consider bidirectional work distributions belonging to the same families, and compare the corresponding bidirectional normalΔFfalse^italicML∗ to the Bennett acceptance ratio (normalΔFfalse^BAR) estimator. We show that, for Gaussian unidirectional work distributions, normalΔFfalse^FD is in fact the parametric MLE of the free energy, and as such, the most efficient estimator for this statistical family. We observe that normalΔFfalse^ML and normalΔFfalse^italicML∗ perform better than normalΔFfalse^J and normalΔFfalse^BAR, for unidirectional and bidirectional distributions, respectively. These results illustrate that the characterization of the underlying work distribution permits an optimal use of the Jarzynski equality. © 2018 Wiley Periodicals, Inc.

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Improving Efficiency in SMD Simulations Through a Hybrid Differential Relaxation Algorithm

Cited by 19 publications

References 43 publications

Computation of Hydration Free Energies Using the Multiple Environment Single System Quantum Mechanical/Molecular Mechanical Method

Computation of Hydration Free Energies Using the Multiple Environment Single System Quantum Mechanical/Molecular Mechanical Method

Efficient Calculation of Enzyme Reaction Free Energy Profiles Using a Hybrid Differential Relaxation Algorithm

On the accurate estimation of free energies using the jarzynski equality

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