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MM/GBSA and LIE estimates of host-guest affinities: dependence on charges and solvation model.

Genheden, Samuel LU (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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Computer-Aided Molecular Design
volume
25
issue
11
pages
1085 - 1093
publisher
Kluwer
external identifiers
  • wos:000298191200007
  • pmid:22101362
  • scopus:84855205990
ISSN
1573-4951
DOI
10.1007/s10822-011-9486-1
language
English
LU publication?
yes
id
18a6f693-3d37-487c-a338-a9ff5ba7c599 (old id 2220582)
date added to LUP
2011-12-13 15:47:59
date last changed
2017-07-09 04:02:45
@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    = {Kluwer},
  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},
  volume       = {25},
  year         = {2011},
}