Random walk in orthogonal space to achieve efficient free-energy simulation of complex systems

In the past few decades, many ingenious efforts have been made in the development of free-energy simulation methods. Because complex systems often undergo nontrivial structural transition during state switching, achieving efficient free-energy calculation can be challenging. As identified earlier, t...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-12, Vol.105 (51), p.20227-20232
Main Authors: Zheng, Lianqing, Chen, Mengen, Yang, Wei
Format: Article
Language:English
Subjects:
Algorithms
Biological Sciences
Chlorides
Complex systems
Computer Simulation
Diffusion
Free energy
Hydrogen-Ion Concentration
Mathematical functions
Methods
Micrococcal Nuclease - chemistry
Micrococcal Nuclease - genetics
Modeling
Models, Chemical
Molecules
Parameter identification
Physical Sciences
Protein Conformation
Random walk
Random walk theory
Recursion
Research design
Simulation
Simulations
Sodium
Thermodynamics
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Summary:In the past few decades, many ingenious efforts have been made in the development of free-energy simulation methods. Because complex systems often undergo nontrivial structural transition during state switching, achieving efficient free-energy calculation can be challenging. As identified earlier, the "Hamiltonian" lagging, which reveals the fact that necessary structural relaxation falls behind the order parameter move, has been a primary problem for generally low free-energy simulation efficiency. Here, we propose an algorithm by achieving a random walk in both the order parameter space and its generalized force space; thereby, the order parameter move and the required conformational relaxation can be efficiently synchronized. As demonstrated in both the alchemical transition and the conformational transition, a leapfrog improvement in free-energy simulation efficiency can be obtained; for instance, (i) it allows us to solve a notoriously challenging problem: accurately predicting the pKa value of a buried titratable residue, Asp-66, in the interior of the V66E staphylococcal nuclease mutant, and (ii) it allows us to gain superior efficiency over the metadynamics algorithm.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0810631106