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

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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.


  • Paulius Mikulskis
  • Samuel Genheden
  • Karin Wichmann
  • Ulf Ryde
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Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Teoretisk kemi
Sidor (från-till)1179-1189
TidskriftJournal of Computational Chemistry
Utgåva nummer12
StatusPublished - 2012
Peer review utfördJa


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Samuel Genheden, 2012, Department of Chemistry, Lund University. 330 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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