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A semiempirical approach to ligand-binding affinities: Dependence on the Hamiltonian and corrections.

Mikulskis, Paulius LU ; Genheden, Samuel LU ; Wichmann, Karin and Ryde, Ulf LU (2012) In Journal of Computational Chemistry 33(12). p.1179-1189
Abstract
We present a combination of semiempirical quantum-mechanical (SQM) calculations in the conductor-like screening model with the MM/GBSA (molecular-mechanics with generalized Born and surface-area solvation) method for ligand-binding affinity calculations. We test three SQM Hamiltonians, AM1, RM1, and PM6, as well as hydrogen-bond corrections and two different dispersion corrections. As test cases, we use the binding of seven biotin analogues to avidin, nine inhibitors to factor Xa, and nine phenol-derivatives to ferritin. The results vary somewhat for the three test cases, but a dispersion correction is mandatory to reproduce experimental estimates. On average, AM1 with the DH2 hydrogen-bond and dispersion corrections gives the best... (More)
We present a combination of semiempirical quantum-mechanical (SQM) calculations in the conductor-like screening model with the MM/GBSA (molecular-mechanics with generalized Born and surface-area solvation) method for ligand-binding affinity calculations. We test three SQM Hamiltonians, AM1, RM1, and PM6, as well as hydrogen-bond corrections and two different dispersion corrections. As test cases, we use the binding of seven biotin analogues to avidin, nine inhibitors to factor Xa, and nine phenol-derivatives to ferritin. The results vary somewhat for the three test cases, but a dispersion correction is mandatory to reproduce experimental estimates. On average, AM1 with the DH2 hydrogen-bond and dispersion corrections gives the best results, which are similar to those of standard MM/GBSA calculations for the same systems. The total time consumption is only 1.3-1.6 times larger than for MM/GBSA. © 2012 Wiley Periodicals, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Computational Chemistry
volume
33
issue
12
pages
1179 - 1189
publisher
John Wiley & Sons
external identifiers
  • wos:000302721300002
  • pmid:22396176
  • scopus:84860835748
ISSN
1096-987X
DOI
10.1002/jcc.22949
language
English
LU publication?
yes
id
4d55ab08-22e7-425b-acfe-4d31d3ed54c7 (old id 2432188)
date added to LUP
2012-04-12 17:12:49
date last changed
2017-09-24 04:00:01
@article{4d55ab08-22e7-425b-acfe-4d31d3ed54c7,
  abstract     = {We present a combination of semiempirical quantum-mechanical (SQM) calculations in the conductor-like screening model with the MM/GBSA (molecular-mechanics with generalized Born and surface-area solvation) method for ligand-binding affinity calculations. We test three SQM Hamiltonians, AM1, RM1, and PM6, as well as hydrogen-bond corrections and two different dispersion corrections. As test cases, we use the binding of seven biotin analogues to avidin, nine inhibitors to factor Xa, and nine phenol-derivatives to ferritin. The results vary somewhat for the three test cases, but a dispersion correction is mandatory to reproduce experimental estimates. On average, AM1 with the DH2 hydrogen-bond and dispersion corrections gives the best results, which are similar to those of standard MM/GBSA calculations for the same systems. The total time consumption is only 1.3-1.6 times larger than for MM/GBSA. © 2012 Wiley Periodicals, Inc.},
  author       = {Mikulskis, Paulius and Genheden, Samuel and Wichmann, Karin and Ryde, Ulf},
  issn         = {1096-987X},
  language     = {eng},
  number       = {12},
  pages        = {1179--1189},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Computational Chemistry},
  title        = {A semiempirical approach to ligand-binding affinities: Dependence on the Hamiltonian and corrections.},
  url          = {http://dx.doi.org/10.1002/jcc.22949},
  volume       = {33},
  year         = {2012},
}