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A semiempirical approach to ligand‐binding affinities: Dependence on the Hamiltonian and corrections
Author(s) -
Mikulskis Paulius,
Genheden Samuel,
Wichmann Karin,
Ryde Ulf
Publication year - 2012
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.22949
Subject(s) - hamiltonian (control theory) , implicit solvation , affinities , solvation , hydrogen bond , bond length , binding energy , chemistry , london dispersion force , computational chemistry , dispersion (optics) , wave function , ligand (biochemistry) , molecular mechanics , physics , stereochemistry , quantum mechanics , molecule , molecular dynamics , mathematics , organic chemistry , mathematical optimization , van der waals force , receptor , biochemistry
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.