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

Research output: Contribution to journalArticle

Standard

A semiempirical approach to ligand-binding affinities: Dependence on the Hamiltonian and corrections. / Mikulskis, Paulius; Genheden, Samuel; Wichmann, Karin; Ryde, Ulf.

In: Journal of Computational Chemistry, Vol. 33, No. 12, 2012, p. 1179-1189.

Research output: Contribution to journalArticle

Harvard

APA

CBE

MLA

Vancouver

Author

Mikulskis, Paulius ; Genheden, Samuel ; Wichmann, Karin ; Ryde, Ulf. / A semiempirical approach to ligand-binding affinities: Dependence on the Hamiltonian and corrections. In: Journal of Computational Chemistry. 2012 ; Vol. 33, No. 12. pp. 1179-1189.

RIS

TY - JOUR

T1 - A semiempirical approach to ligand-binding affinities: Dependence on the Hamiltonian and corrections.

AU - Mikulskis, Paulius

AU - Genheden, Samuel

AU - Wichmann, Karin

AU - Ryde, Ulf

N1 - 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)

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1002/jcc.22949

DO - 10.1002/jcc.22949

M3 - Article

VL - 33

SP - 1179

EP - 1189

JO - Journal of Computational Chemistry

T2 - Journal of Computational Chemistry

JF - Journal of Computational Chemistry

SN - 1096-987X

IS - 12

ER -