Free-energy calculations along a high-dimensional fragmented path with constrained dynamics

Chen, Changjun; Huang, Yanzhao; Xiao, Yi

doi:10.1103/physreve.86.031901

Cited by 9 publications

(21 citation statements)

References 77 publications

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“…In this work, a fragmental path-based constrained dynamic is applied to the binding free-energy calculation [16]. The predefined path directly connects the bound and unbound state of the loop-calcium complex.…”

Section: Resultsmentioning

confidence: 99%

“…More information about its implementation can be found in our previous paper [16]. The constrained dynamics has been developed for many years [38][39][40][41][42][43][44].…”

Section: A Constrained Simulation Along a Path Composed Of Fragmentsmentioning

confidence: 99%

“…For each fragment of the path (between successive snapshots), the free-energy difference can be expressed in a finite difference form [16]:…”

Section: A Constrained Simulation Along a Path Composed Of Fragmentsmentioning

confidence: 99%

“…Recently, we implemented a method based on constrained dynamics, which integrates the free-energy differences along a predefined high-dimensional fragmental path [16]. This strategy can handle free-energy calculations for molecules in different metastable states, and shows better convergence than the conventional free-energy perturbation method.…”

Section: Introductionmentioning

confidence: 99%

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Binding free-energy calculation of an ion-peptide complex by constrained dynamics

et al. 2013

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Binding free energy is the most important physical parameter that describes the binding affinity of a receptor-ligand complex. Conventionally, it was obtained based on the thermodynamic cycle or alchemical reaction. These strategies have been widely used, but they would be problematic if the receptors and/or ligands have large conformational changes during the binding processes. In this paper, we present a way to calculate the binding free energy: constrained dynamics along a fragmental and high-dimensional transition path. This method directly considers unbound states in the simulation. The application to the calmodulin loop-calcium complexes shows that it is practical and the calculated relative binding affinities are in good agreement with experimental results.

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Section: Resultsmentioning

confidence: 99%

“…More information about its implementation can be found in our previous paper [16]. The constrained dynamics has been developed for many years [38][39][40][41][42][43][44].…”

Section: A Constrained Simulation Along a Path Composed Of Fragmentsmentioning

confidence: 99%

“…For each fragment of the path (between successive snapshots), the free-energy difference can be expressed in a finite difference form [16]:…”

Section: A Constrained Simulation Along a Path Composed Of Fragmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Binding free-energy calculation of an ion-peptide complex by constrained dynamics

et al. 2013

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“…The free energies are calculated by Eq 6 [26]. The reaction coordinate ξ on the x -axis represents the location on the path.…”

Section: Resultsmentioning

confidence: 99%

Fast exploration of an optimal path on the multidimensional free energy surface

Chen

2017

PLoS ONE

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In a reaction, determination of an optimal path with a high reaction rate (or a low free energy barrier) is important for the study of the reaction mechanism. This is a complicated problem that involves lots of degrees of freedom. For simple models, one can build an initial path in the collective variable space by the interpolation method first and then update the whole path constantly in the optimization. However, such interpolation method could be risky in the high dimensional space for large molecules. On the path, steric clashes between neighboring atoms could cause extremely high energy barriers and thus fail the optimization. Moreover, performing simulations for all the snapshots on the path is also time-consuming. In this paper, we build and optimize the path by a growing method on the free energy surface. The method grows a path from the reactant and extends its length in the collective variable space step by step. The growing direction is determined by both the free energy gradient at the end of the path and the direction vector pointing at the product. With fewer snapshots on the path, this strategy can let the path avoid the high energy states in the growing process and save the precious simulation time at each iteration step. Applications show that the presented method is efficient enough to produce optimal paths on either the two-dimensional or the twelve-dimensional free energy surfaces of different small molecules.

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Walking freely in the energy and temperature space by the modified replica exchange molecular dynamics method

Chen

Huang

2016

J. Comput. Chem.

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Replica Exchange Molecular Dynamics (REMD) method is a powerful sampling tool in molecular simulations. Recently, we made a modification to the standard REMD method. It places some inactive replicas at different temperatures as well as the active replicas. The method completely decouples the number of the active replicas and the number of the temperature levels. In this article, we make a further modification to our previous method. It uses the inactive replicas in a different way. The inactive replicas first sample in their own knowledge-based energy databases and then participate in the replica exchange operations in the REMD simulation. In fact, this method is a hybrid between the standard REMD method and the simulated tempering method. Using different active replicas, one can freely control the calculation quantity and the convergence speed of the simulation. To illustrate the performance of the method, we apply it to some small models. The distribution functions of the replicas in the energy space and temperature space show that the modified REMD method in this work can let the replicas walk freely in both of the two spaces. With the same number of the active replicas, the free energy surface in the simulation converges faster than the standard REMD. © 2016 Wiley Periodicals, Inc.

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Free-energy calculations along a high-dimensional fragmented path with constrained dynamics

Cited by 9 publications

References 77 publications

Binding free-energy calculation of an ion-peptide complex by constrained dynamics

Binding free-energy calculation of an ion-peptide complex by constrained dynamics

Fast exploration of an optimal path on the multidimensional free energy surface

Walking freely in the energy and temperature space by the modified replica exchange molecular dynamics method

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