Computing conformational free energy differences in explicit solvent : An efficient thermodynamic cycle using an auxiliary potential and a free energy functional constructed from the end points

© 2016 Wiley Periodicals, Inc.

Bibliographische Detailangaben
Veröffentlicht in:Journal of computational chemistry. - 1984. - 38(2017), 15 vom: 05. Juni, Seite 1198-1208
1. Verfasser: Harris, Robert C (VerfasserIn)
Weitere Verfasser: Deng, Nanjie, Levy, Ronald M, Ishizuka, Ryosuke, Matubayasi, Nobuyuki
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2017
Zugriff auf das übergeordnete Werk:Journal of computational chemistry
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. conformational changes distribution function energy representation molecular dynamics simulations solvation free energy Dipeptides mehr... Solvents beta-Cyclodextrins Water 059QF0KO0R alanylalanine 2867-20-1 betadex JV039JZZ3A
Beschreibung
Zusammenfassung:© 2016 Wiley Periodicals, Inc.
Many biomolecules undergo conformational changes associated with allostery or ligand binding. Observing these changes in computer simulations is difficult if their timescales are long. These calculations can be accelerated by observing the transition on an auxiliary free energy surface with a simpler Hamiltonian and connecting this free energy surface to the target free energy surface with free energy calculations. Here, we show that the free energy legs of the cycle can be replaced with energy representation (ER) density functional approximations. We compute: (1) The conformational free energy changes for alanine dipeptide transitioning from the right-handed free energy basin to the left-handed basin and (2) the free energy difference between the open and closed conformations of β-cyclodextrin, a "host" molecule that serves as a model for molecular recognition in host-guest binding. β-cyclodextrin contains 147 atoms compared to 22 atoms for alanine dipeptide, making β-cyclodextrin a large molecule for which to compute solvation free energies by free energy perturbation or integration methods and the largest system for which the ER method has been compared to exact free energy methods. The ER method replaced the 28 simulations to compute each coupling free energy with two endpoint simulations, reducing the computational time for the alanine dipeptide calculation by about 70% and for the β-cyclodextrin by > 95%. The method works even when the distribution of conformations on the auxiliary free energy surface differs substantially from that on the target free energy surface, although some degree of overlap between the two surfaces is required. © 2016 Wiley Periodicals, Inc
Beschreibung:Date Completed 17.05.2019
Date Revised 17.05.2019
published: Print-Electronic
Citation Status MEDLINE
ISSN:1096-987X
DOI:10.1002/jcc.24668