| Abstract
| - The free energy of binding between avidin and seven biotin analogues has been calculated with the molecularmechanics Poisson−Boltzmann surface area (MM/PBSA) method. We have studied how the force fieldand the method to generate geometries affect the calculated binding free energies. Four different force fieldswere compared, but we saw no significant difference in the results. However, mixing the force fields usedfor the geometry generation and energy calculations is not recommended. In the molecular dynamicssimulations, explicit water molecules must be used, but the size of the simulated system and the boundaryconditions are less important. In fact, nonperiodic simulations with a fixed protein outside a relatively smallsimulated system (18 Å) seem to be a proper approach. The mean absolute error was 9−19 kJ/mol, with astandard error of 5−15 kJ/mol, which arises mainly from the entropy term.
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