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Replica-Exchange Accelerated Molecular Dynamics (REXAMD) Applied to Thermodynamic Integration.

Fajer M, Hamelberg D, McCammon JA - J Chem Theory Comput (2008)

Bottom Line: Accelerated molecular dynamics (AMD) is an efficient strategy for accelerating the sampling of molecular dynamics simulations, and observable quantities such as free energies derived on the biased AMD potential can be reweighted to yield results consistent with the original, unmodified potential.We propose a replica exchange of various degrees of acceleration (REXAMD) to retain good statistics while achieving enhanced sampling.The REXAMD method is validated and benchmarked on two simple gas-phase model systems, and two different strategies for computing reweighted averages over a simulation are compared.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0365, Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, California 92039-0365, Department of Chemistry, Georgia State University, Atlanta, Georgia 30302-4098, Department of Pharmacology, University of California at San Diego, La Jolla, California 92093-0365, and Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92093-0365.

ABSTRACT
Accelerated molecular dynamics (AMD) is an efficient strategy for accelerating the sampling of molecular dynamics simulations, and observable quantities such as free energies derived on the biased AMD potential can be reweighted to yield results consistent with the original, unmodified potential. In conventional AMD the reweighting procedure has an inherent statistical problem in systems with large acceleration, where the points with the largest biases will dominate the reweighted result and reduce the effective number of data points. We propose a replica exchange of various degrees of acceleration (REXAMD) to retain good statistics while achieving enhanced sampling. The REXAMD method is validated and benchmarked on two simple gas-phase model systems, and two different strategies for computing reweighted averages over a simulation are compared.

No MeSH data available.


Structure of the model systems (A) and (B). The Dm atoms indicate a dummy atom with no nonbonded interactions.
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fig1: Structure of the model systems (A) and (B). The Dm atoms indicate a dummy atom with no nonbonded interactions.

Mentions: Two model systems were studied to validate and benchmark the REXAMD method. Both model systems are symmetric alchemical mutations where the product has an identical structure to the reactant, and thus the ΔG is zero and independent of the force field. Model system A (MSA) is a gas-phase alchemical mutation from ethane-to-ethane (Figure 1A). This system will serve as a positive control to show that REXAMD can reproduce the results of an ergodic regular molecular dynamics simulation. The relative simplicity of the system and the low transition barriers guarantees that the regular molecular dynamics (REXREG) is able to sample the entire conformational space in a short time scale. The thermodynamic integration for MSA uses a 9-point Gaussian quadrature. The MSA REXAMDt simulations used only two replicas: an unmodified potential and an accelerated potential with a torsional boost (Ecut of 5.0 kcal mol−1, α of 2.0 kcal mol−1). Each run was simulated for 8 million MD steps or the equivalent of 8 ns for an unmodified potential.


Replica-Exchange Accelerated Molecular Dynamics (REXAMD) Applied to Thermodynamic Integration.

Fajer M, Hamelberg D, McCammon JA - J Chem Theory Comput (2008)

Structure of the model systems (A) and (B). The Dm atoms indicate a dummy atom with no nonbonded interactions.
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651661&req=5

fig1: Structure of the model systems (A) and (B). The Dm atoms indicate a dummy atom with no nonbonded interactions.
Mentions: Two model systems were studied to validate and benchmark the REXAMD method. Both model systems are symmetric alchemical mutations where the product has an identical structure to the reactant, and thus the ΔG is zero and independent of the force field. Model system A (MSA) is a gas-phase alchemical mutation from ethane-to-ethane (Figure 1A). This system will serve as a positive control to show that REXAMD can reproduce the results of an ergodic regular molecular dynamics simulation. The relative simplicity of the system and the low transition barriers guarantees that the regular molecular dynamics (REXREG) is able to sample the entire conformational space in a short time scale. The thermodynamic integration for MSA uses a 9-point Gaussian quadrature. The MSA REXAMDt simulations used only two replicas: an unmodified potential and an accelerated potential with a torsional boost (Ecut of 5.0 kcal mol−1, α of 2.0 kcal mol−1). Each run was simulated for 8 million MD steps or the equivalent of 8 ns for an unmodified potential.

Bottom Line: Accelerated molecular dynamics (AMD) is an efficient strategy for accelerating the sampling of molecular dynamics simulations, and observable quantities such as free energies derived on the biased AMD potential can be reweighted to yield results consistent with the original, unmodified potential.We propose a replica exchange of various degrees of acceleration (REXAMD) to retain good statistics while achieving enhanced sampling.The REXAMD method is validated and benchmarked on two simple gas-phase model systems, and two different strategies for computing reweighted averages over a simulation are compared.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0365, Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, California 92039-0365, Department of Chemistry, Georgia State University, Atlanta, Georgia 30302-4098, Department of Pharmacology, University of California at San Diego, La Jolla, California 92093-0365, and Howard Hughes Medical Institute, University of California at San Diego, La Jolla, California 92093-0365.

ABSTRACT
Accelerated molecular dynamics (AMD) is an efficient strategy for accelerating the sampling of molecular dynamics simulations, and observable quantities such as free energies derived on the biased AMD potential can be reweighted to yield results consistent with the original, unmodified potential. In conventional AMD the reweighting procedure has an inherent statistical problem in systems with large acceleration, where the points with the largest biases will dominate the reweighted result and reduce the effective number of data points. We propose a replica exchange of various degrees of acceleration (REXAMD) to retain good statistics while achieving enhanced sampling. The REXAMD method is validated and benchmarked on two simple gas-phase model systems, and two different strategies for computing reweighted averages over a simulation are compared.

No MeSH data available.