Alchemical free energy calculations and multiple conformational substates

Thermodynamic integration (TI) was combined with (adaptive) umbrella sampling to improve the convergence of alchemical free energy simulations in which multiple conformational substates are present. The approach, which we refer to as non-Boltzmann TI (NBTI), was tested by computing the free energy d...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of chemical physics 2005-02, Vol.122 (8), p.84109-84109
Main Authors: Leitgeb, Martin, Schröder, Christian, Boresch, Stefan
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Thermodynamic integration (TI) was combined with (adaptive) umbrella sampling to improve the convergence of alchemical free energy simulations in which multiple conformational substates are present. The approach, which we refer to as non-Boltzmann TI (NBTI), was tested by computing the free energy differences between three five-atomic model systems, as well as the free energy difference of solvation between leucine and asparagine. In both cases regular TI failed to give converged results, whereas the NBTI results were free from hysteresis and had standard deviations well below +/-0.7 kcal/mole. We also present theoretical considerations that make it possible to compute free energy differences between simple molecules, such as the five-atomic model systems, by numerical integration of the partition functions at the respective end points.
ISSN:0021-9606
1089-7690
DOI:10.1063/1.1850900