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Replica exchange enveloping distribution sampling (RE-EDS): A robust method to estimate multiple free-energy differences from a single simulation
- Source :
- The Journal of chemical physics. 145(15)
- Publication Year :
- 2016
-
Abstract
- In molecular dynamics (MD) simulations, free-energy differences are often calculated using free energy perturbation or thermodynamic integration (TI) methods. However, both techniques are only suited to calculate free-energy differences between two end states. Enveloping distribution sampling (EDS) presents an attractive alternative that allows to calculate multiple free-energy differences in a single simulation. In EDS, a reference state is simulated which "envelopes" the end states. The challenge of this methodology is the determination of optimal reference-state parameters to ensure equal sampling of all end states. Currently, the automatic determination of the reference-state parameters for multiple end states is an unsolved issue that limits the application of the methodology. To resolve this, we have generalised the replica-exchange EDS (RE-EDS) approach, introduced by Lee et al. [J. Chem. Theory Comput. 10, 2738 (2014)] for constant-pH MD simulations. By exchanging configurations between replicas with different reference-state parameters, the complexity of the parameter-choice problem can be substantially reduced. A new robust scheme to estimate the reference-state parameters from a short initial RE-EDS simulation with default parameters was developed, which allowed the calculation of 36 free-energy differences between nine small-molecule inhibitors of phenylethanolamine N-methyltransferase from a single simulation. The resulting free-energy differences were in excellent agreement with values obtained previously by TI and two-state EDS simulations.
- Subjects :
- 100 Philosophy
010304 chemical physics
Chemistry
Replica
Phenylethanolamine N-Methyltransferase
General Physics and Astronomy
Sampling (statistics)
Thermodynamic integration
State (functional analysis)
Molecular Dynamics Simulation
010402 general chemistry
01 natural sciences
10092 Institute of Philosophy
3100 General Physics and Astronomy
0104 chemical sciences
Free energy perturbation
Small Molecule Libraries
Molecular dynamics
Distribution (mathematics)
0103 physical sciences
Thermodynamics
Statistical physics
Physical and Theoretical Chemistry
1606 Physical and Theoretical Chemistry
Energy (signal processing)
Subjects
Details
- ISSN :
- 10897690
- Volume :
- 145
- Issue :
- 15
- Database :
- OpenAIRE
- Journal :
- The Journal of chemical physics
- Accession number :
- edsair.doi.dedup.....0167c541a9b1967b2d0cfb2228261309