Journal Article

FZJ-2021-01554

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Ligand Affinities within the Open-Boundary Molecular Mechanics/Coarse-Grained Framework (I): Alchemical Transformations within the Hamiltonian Adaptive Resolution Scheme

Korshunova, K.FZJ* ; Carloni, P. (Corresponding author)FZJ*

2021
Soc. Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/27578  doi:10.1021/acs.jpcb.0c09805

Abstract: Our recently developed Open-Boundary Molecular Mechanics/Coarse Grained (OB-MM/CG) framework predicts ligand poses in important pharmaceutical targets, such as G-protein Coupled Receptors, even when experimental structural information is lacking. The approach, which is based on GROMOS and AMBER force fields, allows for grand-canonical simulations of protein–ligand complexes by using the Hamiltonian Adaptive Resolution Scheme (H-AdResS) for the solvent. Here, we present a key step toward the estimation of ligand binding affinities for their targets within this approach. This is the implementation of the H-AdResS in the GROMACS code. The accuracy of our implementation is established by calculating hydration free energies of several molecules in water by means of alchemical transformations. The deviations of the GROMOS- and AMBER-based H-AdResS results from the reference fully atomistic simulations are smaller than the accuracy of the force field and/or they are in the range of the published results. Importantly, our predictions are in good agreement with experimental data. The current implementation paves the way to the use of the OB-MM/CG framework for the study of large biological systems.

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Contributing Institute(s):

1. Computational Biomedicine (IAS-5)
2. Computational Biomedicine (INM-9)

Research Program(s):

1. 524 - Molecular and Cellular Information Processing (POF4-524) (POF4-524)

Appears in the scientific report 2021

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Database coverage:
; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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