Ligand affinities predicted with the MM/PBSA method: dependence on the simulation method and the force field.
The free energy of binding between avidin and seven biotin analogues has been calculated with the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) method. We have studied how the force field and the method to generate geometries affect the calculated binding free energies. Four different force fields were compared, but we saw no significant difference in the results. However, mixing the force fields used for the geometry generation and energy calculations is not recommended. In the molecular dynamics simulations, explicit water molecules must be used, but the size of the simulated system and the boundary conditions are less important. In fact, nonperiodic simulations with a fixed protein outside a relatively small simulated system (18 A) seem to be a proper approach. The mean absolute error was 9-19 kJ/mol, with a standard error of 5-15 kJ/mol, which arises mainly from the entropy term.
Weis
Aaron
A
Department of Theoretical Chemistry, Lund University, Chemical Centre, P.O. Box 124, SE-221 00 Lund, Sweden.
Katebzadeh
Kambiz
K
Söderhjelm
Pär
P
Nilsson
Ingemar
I
Ryde
Ulf
U
D000465:Algorithms; D001360:Avidin / Q000737:chemistry*; D001710:Biotin / Q000031:analogs & derivatives* / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D004563:Electrochemistry; D004574:Electromagnetic Fields; D019277:Entropy; D019791:Guanidine / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D016012:Poisson Distribution; D013499:Surface Properties; D009626:Terminology as Topic; D014961:X-Ray Diffraction
D008024:Ligands; D001360:Avidin; D001710:Biotin; D019791:Guanidine