Optimization of replica exchange molecular dynamics by fast mimicking

Hritz, Jozef; Oostenbrink, Chris

doi:10.1063/1.2790427

Cited by 31 publications

(68 citation statements)

References 25 publications

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“…[8][9][10][11][12][13][14][15][16][17][18][19] An important result obtained by Sindhikara et al 8 is that exchange attempts are best chosen as frequently as possible. Similar conclusions were obtained by Abraham and Gready 17 based on analyzing the autocorrelation function of the potential energy.…”

Section: Introductionmentioning

confidence: 99%

“…Such an approach has been pursued by Hritz and Oostenbrink. 12 Replica exchange rates can be obtained from the attempt frequencies and acceptance rates. The latter can be estimated from the energy distributions in the folded and unfolded states at the different temperatures ͑from simulation at some temperatures and interpolation at others͒.…”

Section: Equilibrationmentioning

confidence: 99%

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Error and efficiency of replica exchange molecular dynamics simulations

Rosta

Hummer

2009

The Journal of Chemical Physics

152

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We derive simple analytical expressions for the error and computational efficiency of replica exchange molecular dynamics ͑REMD͒ simulations ͑and by analogy replica exchange Monte Carlo simulations͒. The theory applies to the important case of systems whose dynamics at long times is dominated by the slow interconversion between two metastable states. As a specific example, we consider the folding and unfolding of a protein. The efficiency is defined as the rate with which the error in an estimated equilibrium property, as measured by the variance of the estimator over repeated simulations, decreases with simulation time. For two-state systems, this rate is in general independent of the particular property. Our main result is that, with comparable computational resources used, the relative efficiency of REMD and molecular dynamics ͑MD͒ simulations is given by the ratio of the number of transitions between the two states averaged over all replicas at the different temperatures, and the number of transitions at the single temperature of the MD run. This formula applies if replica exchange is frequent, as compared to the transition times. High efficiency of REMD is thus achieved by including replica temperatures in which the frequency of transitions is higher than that at the temperature of interest. In tests of the expressions for the error in the estimator, computational efficiency, and the rate of equilibration we find quantitative agreement with the results both from kinetic models of REMD and from actual all-atom simulations of the folding of a peptide in water.

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Section: Introductionmentioning

confidence: 99%

Section: Equilibrationmentioning

confidence: 99%

Error and efficiency of replica exchange molecular dynamics simulations

Rosta

Hummer

2009

The Journal of Chemical Physics

152

View full text Add to dashboard Cite

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“…Conditions ͑ or T͒ do not have to be different for all replicas. In a degenerate max / T max scheme, 11 multiple replicas are simulated at the same max / T max simultaneously, i.e., m͑i͒ = m͑j͒. At regular time intervals we attempt to exchange ͑switch͒ the conditions at which replicas i , j are simulated,…”

Section: B Remdmentioning

confidence: 99%

“…11 In this approach more replicas ͑n͒ are simulated at the highest -value, max , simultaneously and the time between switching attempts between these replicas is set such that every replica at max spends a time t max total , during which the system can convert from one conformation to the other. Usually t max total ӷ t elem because the conversion probability rather shows a sigmoidal than a linear time dependence, and the middle of the sigmoidal curve corresponds to a significantly longer time than t elem .…”

Section: MD and Remd Settingsmentioning

confidence: 99%

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Hamiltonian replica exchange molecular dynamics using soft-core interactions

Hritz

Oostenbrink

2008

The Journal of Chemical Physics

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132

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To overcome the problem of insufficient conformational sampling within biomolecular simulations, we have developed a novel Hamiltonian replica exchange molecular dynamics ͑H-REMD͒ scheme that uses soft-core interactions between those parts of the system that contribute most to high energy barriers. The advantage of this approach over other H-REMD schemes is the possibility to use a relatively small number of replicas with locally larger differences between the individual Hamiltonians. Because soft-core potentials are almost the same as regular ones at longer distances, most of the interactions between atoms of perturbed parts will only be slightly changed. Rather, the strong repulsion between atoms that are close in space, which in many cases results in high energy barriers, is weakened within higher replicas of our proposed scheme. In addition to the soft-core interactions, we proposed to include multiple replicas using the same Hamiltonian/level of softness. We have tested the new protocol on the GTP and 8-Br-GTP molecules, which are known to have high energy barriers between the anti and syn conformation of the base with respect to the sugar moiety. During two 25 ns MD simulations of both systems the transition from the more stable to the less stable ͑but still experimentally observed͒ conformation is not seen at all. Also temperature REMD over 50 replicas for 1 ns did not show any transition at room temperature. On the other hand, more than 20 of such transitions are observed in H-REMD using six replicas ͑at three different Hamiltonians͒ during 6.8 ns per replica for GTP and 12 replicas ͑at six different Hamiltonians͒ during 8.7 ns per replica for 8-Br-GTP. The large increase in sampling efficiency was obtained from an optimized H-REMD scheme involving soft-core potentials, with multiple simulations using the same level of softness. The optimization of the scheme was performed by fast mimicking ͓J. Hritz and C. Oostenbrink, J. Chem. Phys. 127, 204104 ͑2007͔͒.

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Free‐energy differences between states with different conformational ensembles

Gárate

Oostenbrink

2013

J Comput Chem

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Multiple conformations separated by high-energy barriers represent a challenging problem in free-energy calculations due to the difficulties in achieving adequate sampling. We present an application of thermodynamic integration (TI) in conjunction with the local elevation umbrella sampling (LE/US) method to improve convergence in alchemical free-energy calculations. TI-LE/US was applied to the guanosine triphosphate (GTP) to 8-Br-GTP perturbation, molecules that present high-energy barriers between the anti and syn states and that have inverted preferences for those states. The convergence and reliability of TI-LE/US was assessed by comparing with previous results using the enhanced-sampling one-step perturbation (OSP) method. A linear interpolation of the end-state biasing potentials was sufficient to dramatically improve sampling along the chosen reaction coordinate. Conformational free-energy differences were also computed for the syn and anti states and compared to experimental and theoretical results. Additionally, a coupled OSP with LE/US was carried out, allowing the calculation of conformational and alchemical free energies of GTP and 8-substituted GTP analogs.

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Optimization of replica exchange molecular dynamics by fast mimicking

Cited by 31 publications

References 25 publications

Error and efficiency of replica exchange molecular dynamics simulations

Error and efficiency of replica exchange molecular dynamics simulations

Hamiltonian replica exchange molecular dynamics using soft-core interactions

Free‐energy differences between states with different conformational ensembles

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