MM/GBSA and LIE estimates of host-guest affinities: dependence on charges and solvation model.
(2011) In Journal of Computer-Aided Molecular Design 25(11). p.1085-1093- Abstract
- The affinities of two sets of guest-host systems were estimated using the popular end-point methods MM/GBSA (molecular-mechanics with generalised Born and surface-area solvation) and LIE (linear interaction energy). A set of six primary alcohols that bind to α-cyclodextrin (α-CD) and a set of eight guest molecules to cucurbit[8]uril (CB8) were considered. Three different charge schemes were used to obtain charges for the host and guest molecules, viz., AM1-BCC, RESP, and the recently suggested xAvESP (which average ESP charges over a number of molecular dynamics snapshots). Furthermore, both the generalised Born and Poisson-Boltzmann solvation models were used in the MM/GBSA calculations. The two solvation models perform equally well in... (More)
- The affinities of two sets of guest-host systems were estimated using the popular end-point methods MM/GBSA (molecular-mechanics with generalised Born and surface-area solvation) and LIE (linear interaction energy). A set of six primary alcohols that bind to α-cyclodextrin (α-CD) and a set of eight guest molecules to cucurbit[8]uril (CB8) were considered. Three different charge schemes were used to obtain charges for the host and guest molecules, viz., AM1-BCC, RESP, and the recently suggested xAvESP (which average ESP charges over a number of molecular dynamics snapshots). Furthermore, both the generalised Born and Poisson-Boltzmann solvation models were used in the MM/GBSA calculations. The two solvation models perform equally well in predicting relative affinities, and hence there is no point in using the more expensive Poisson-Boltzmann model for these systems. Both the LIE and MM/GBSA estimates are shown to be robust with respect to the charge model, and therefore it is recommended to use the cheapest AM1-BCC charges. Using AM1-BCC charges, the MM/GBSA method gave a MADtr (mean absolute deviation after removal of systematic error) of 17 kJ/mol and a correlation coefficient (r (2)) of 0.67 for the CB8 complexes, and a MADtr of 10 kJ/mol and an r (2) of 0.96 for the α-CD complexes. The LIE method gave a MADtr of 20 kJ/mol and an r (2) of 0.10 for the CB8 complexes, after optimisation of the non-polar scaling parameter. For the α-CD complexes, no optimisation was necessary and the method gave a MADtr of 2 kJ/mol and a r (2) of 0.96. These results indicate that both MM/GBSA and LIE are able to estimate host-guest affinities accurately. (Less)
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https://lup.lub.lu.se/record/2220582
- author
- Genheden, Samuel LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Computer-Aided Molecular Design
- volume
- 25
- issue
- 11
- pages
- 1085 - 1093
- publisher
- Springer
- external identifiers
-
- wos:000298191200007
- pmid:22101362
- scopus:84855205990
- ISSN
- 1573-4951
- DOI
- 10.1007/s10822-011-9486-1
- 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
- 18a6f693-3d37-487c-a338-a9ff5ba7c599 (old id 2220582)
- date added to LUP
- 2016-04-01 14:04:13
- date last changed
- 2023-01-04 02:29:35
@article{18a6f693-3d37-487c-a338-a9ff5ba7c599,
abstract = {{The affinities of two sets of guest-host systems were estimated using the popular end-point methods MM/GBSA (molecular-mechanics with generalised Born and surface-area solvation) and LIE (linear interaction energy). A set of six primary alcohols that bind to α-cyclodextrin (α-CD) and a set of eight guest molecules to cucurbit[8]uril (CB8) were considered. Three different charge schemes were used to obtain charges for the host and guest molecules, viz., AM1-BCC, RESP, and the recently suggested xAvESP (which average ESP charges over a number of molecular dynamics snapshots). Furthermore, both the generalised Born and Poisson-Boltzmann solvation models were used in the MM/GBSA calculations. The two solvation models perform equally well in predicting relative affinities, and hence there is no point in using the more expensive Poisson-Boltzmann model for these systems. Both the LIE and MM/GBSA estimates are shown to be robust with respect to the charge model, and therefore it is recommended to use the cheapest AM1-BCC charges. Using AM1-BCC charges, the MM/GBSA method gave a MADtr (mean absolute deviation after removal of systematic error) of 17 kJ/mol and a correlation coefficient (r (2)) of 0.67 for the CB8 complexes, and a MADtr of 10 kJ/mol and an r (2) of 0.96 for the α-CD complexes. The LIE method gave a MADtr of 20 kJ/mol and an r (2) of 0.10 for the CB8 complexes, after optimisation of the non-polar scaling parameter. For the α-CD complexes, no optimisation was necessary and the method gave a MADtr of 2 kJ/mol and a r (2) of 0.96. These results indicate that both MM/GBSA and LIE are able to estimate host-guest affinities accurately.}},
author = {{Genheden, Samuel}},
issn = {{1573-4951}},
language = {{eng}},
number = {{11}},
pages = {{1085--1093}},
publisher = {{Springer}},
series = {{Journal of Computer-Aided Molecular Design}},
title = {{MM/GBSA and LIE estimates of host-guest affinities: dependence on charges and solvation model.}},
url = {{http://dx.doi.org/10.1007/s10822-011-9486-1}},
doi = {{10.1007/s10822-011-9486-1}},
volume = {{25}},
year = {{2011}},
}