A semiempirical approach to ligand-binding affinities: Dependence on the Hamiltonian and corrections.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2432188
- author
- Mikulskis, Paulius LU ; Genheden, Samuel LU ; Wichmann, Karin and Ryde, Ulf LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Computational Chemistry
- volume
- 33
- issue
- 12
- pages
- 1179 - 1189
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000302721300002
- pmid:22396176
- scopus:84860835748
- pmid:22396176
- ISSN
- 1096-987X
- DOI
- 10.1002/jcc.22949
- 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
- 4d55ab08-22e7-425b-acfe-4d31d3ed54c7 (old id 2432188)
- date added to LUP
- 2016-04-01 13:44:04
- date last changed
- 2023-03-19 03:32:08
@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 Inc.}}, series = {{Journal of Computational Chemistry}}, title = {{A semiempirical approach to ligand-binding affinities: Dependence on the Hamiltonian and corrections.}}, url = {{https://lup.lub.lu.se/search/files/3559070/3412381.pdf}}, doi = {{10.1002/jcc.22949}}, volume = {{33}}, year = {{2012}}, }