BAR-based optimum adaptive sampling regime for variance minimization in alchemical transformation

Zhao X. Sun, Xiao H. Wang, John Zhang

Research output: Contribution to journalArticle

Abstract

The efficiency of alchemical free energy simulations with the staging strategy is improved by adaptively manipulating the significance of each ensemble followed by importance sampling. The OBAR (optimum BAR) method introduced in this work with explicit consideration of the statistical inefficiency in each ensemble outperforms the traditional equal time rule which is used in standard applications of alchemical transformation with the window sampling regime in the sense of minimizing the total variance of the free energy estimate. The Time Derivative of total Variance (TDV) is proposed for the OBAR criterion which is linearly dependent on the variance and is more sensitive to the importance rank than the overlap matrix. The performance of OBAR workflow is demonstrated for solvation of several small molecules and a protein ligand binding system.

Original languageEnglish (US)
Pages (from-to)15005-15020
Number of pages16
JournalPhysical Chemistry Chemical Physics
Volume19
Issue number23
DOIs
StatePublished - 2017

Fingerprint

Free energy
sampling
Sampling
Importance sampling
optimization
Solvation
free energy
Ligands
Derivatives
Molecules
solvation
proteins
ligands
Proteins
estimates
matrices
molecules
simulation

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry

Cite this

BAR-based optimum adaptive sampling regime for variance minimization in alchemical transformation. / Sun, Zhao X.; Wang, Xiao H.; Zhang, John.

In: Physical Chemistry Chemical Physics, Vol. 19, No. 23, 2017, p. 15005-15020.

Research output: Contribution to journalArticle

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