Effect of explicit water molecules on ligand-binding affinities calculated with the MM/GBSA approach.
Mikulskis, Paulius LU ; Genheden, Samuel LU and Ryde, Ulf LU
(2014)
In Journal of Molecular Modeling
20(6).
p.2273-2273
- Abstract
- We tested different approaches to including the effect of binding-site water molecules for ligand-binding affinities within the MM/GBSA approach (molecular mechanics combined with generalised Born and surface-area solvation). As a test case, we studied the binding of nine phenol analogues to ferritin. The effect of water molecules mediating the interaction between the receptor and the ligand can be studied by considering a few water molecules as a part of the receptor. We extended previous methods by allowing for a variable number of water molecules in the binding site. The effect of displaced water molecules can also be considered within the MM/GBSA philosophy by calculating the affinities of binding-site water molecules, both before and... (More)
- We tested different approaches to including the effect of binding-site water molecules for ligand-binding affinities within the MM/GBSA approach (molecular mechanics combined with generalised Born and surface-area solvation). As a test case, we studied the binding of nine phenol analogues to ferritin. The effect of water molecules mediating the interaction between the receptor and the ligand can be studied by considering a few water molecules as a part of the receptor. We extended previous methods by allowing for a variable number of water molecules in the binding site. The effect of displaced water molecules can also be considered within the MM/GBSA philosophy by calculating the affinities of binding-site water molecules, both before and after binding of the ligand. To obtain proper energies, both the water molecules and the ligand need then to be converted to non-interacting ghost molecules and a single-average approach (i.e., the same structures are used for bound and unbound states) based on the simulations of both the complex and the free receptor can be used to improve the precision. The only problem is to estimate the free energy of an unbound water molecule. With an experimental estimate of this parameter, promising results were obtained for our test case. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4452401
- author
- Mikulskis, Paulius
LU
; Genheden, Samuel
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Molecular Modeling
- volume
- 20
- issue
- 6
- pages
- 2273 - 2273
- publisher
- Springer
- external identifiers
-
- pmid:24869780
- wos:000338632200026
- scopus:84901576326
- pmid:24869780
- ISSN
- 1610-2940
- DOI
- 10.1007/s00894-014-2273-x
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)
- id
- 9d69e64e-1164-4592-ba86-f77cf322a334 (old id 4452401)
- date added to LUP
- 2016-04-01 10:37:26
- date last changed
- 2023-01-17 21:39:28
@article{9d69e64e-1164-4592-ba86-f77cf322a334,
abstract = {{We tested different approaches to including the effect of binding-site water molecules for ligand-binding affinities within the MM/GBSA approach (molecular mechanics combined with generalised Born and surface-area solvation). As a test case, we studied the binding of nine phenol analogues to ferritin. The effect of water molecules mediating the interaction between the receptor and the ligand can be studied by considering a few water molecules as a part of the receptor. We extended previous methods by allowing for a variable number of water molecules in the binding site. The effect of displaced water molecules can also be considered within the MM/GBSA philosophy by calculating the affinities of binding-site water molecules, both before and after binding of the ligand. To obtain proper energies, both the water molecules and the ligand need then to be converted to non-interacting ghost molecules and a single-average approach (i.e., the same structures are used for bound and unbound states) based on the simulations of both the complex and the free receptor can be used to improve the precision. The only problem is to estimate the free energy of an unbound water molecule. With an experimental estimate of this parameter, promising results were obtained for our test case.}},
author = {{Mikulskis, Paulius and Genheden, Samuel and Ryde, Ulf}},
issn = {{1610-2940}},
language = {{eng}},
number = {{6}},
pages = {{2273--2273}},
publisher = {{Springer}},
series = {{Journal of Molecular Modeling}},
title = {{Effect of explicit water molecules on ligand-binding affinities calculated with the MM/GBSA approach.}},
url = {{https://lup.lub.lu.se/search/files/2000356/5266647.pdf}},
doi = {{10.1007/s00894-014-2273-x}},
volume = {{20}},
year = {{2014}},
}