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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.


Block average of the MSB thermodynamic integration results from the reweighted periods strategy. The symbols show the average value of each simulation type, and the shaded region shows the standard error for each simulation type.
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fig3: Block average of the MSB thermodynamic integration results from the reweighted periods strategy. The symbols show the average value of each simulation type, and the shaded region shows the standard error for each simulation type.

Mentions: The 20 ns MSB REXAMDtT simulations are well mixed (Table 1, Figures S-I and S-II (Supporting Information)). The regular molecular dynamics (REXREG) was unable to efficiently sample the conformational space (Figure S-III in the Supporting Information) and still shows a substantially nonzero ΔG after the 20 ns for both the reweighted periods and reweighted runs strategies (Table 3). The slow convergence of the REXREG result can also be seen in the block averaging of ΔG in Figure 3. In contrast, the REXAMDtT simulations were able to efficiently sample the conformational space Figure S-IV in the Supporting Information. The ΔG was consistently within 0.1 kcal mol−1 of zero after 2.9 and 5.5 ns for the reweighted periods strategy and the reweighted runs strategy, respectively.


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

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

Block average of the MSB thermodynamic integration results from the reweighted periods strategy. The symbols show the average value of each simulation type, and the shaded region shows the standard error for each simulation type.
© Copyright Policy - open-access - ccc-price
Related In: Results  -  Collection

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

fig3: Block average of the MSB thermodynamic integration results from the reweighted periods strategy. The symbols show the average value of each simulation type, and the shaded region shows the standard error for each simulation type.
Mentions: The 20 ns MSB REXAMDtT simulations are well mixed (Table 1, Figures S-I and S-II (Supporting Information)). The regular molecular dynamics (REXREG) was unable to efficiently sample the conformational space (Figure S-III in the Supporting Information) and still shows a substantially nonzero ΔG after the 20 ns for both the reweighted periods and reweighted runs strategies (Table 3). The slow convergence of the REXREG result can also be seen in the block averaging of ΔG in Figure 3. In contrast, the REXAMDtT simulations were able to efficiently sample the conformational space Figure S-IV in the Supporting Information. The ΔG was consistently within 0.1 kcal mol−1 of zero after 2.9 and 5.5 ns for the reweighted periods strategy and the reweighted runs strategy, respectively.

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.