How transferable are hydrogen parameters in molecular mechanics calculations?

Interactions of water with various methyl hydrogens were studied using ab initio quantum mechanics and molecular mechanics. Our goal was to determine the effect of electronegative substituents on the nonbonded interactions of hydrogens. We found that methyl hydrogens are indeed very much affected by substituents and that standard van der Waals parameters used for these hydrogens in molecular mechanics do not reproduce these effects. Adjusted van der Waals parameters are presented that reproduce the ab initio values, and their use is discussed, as well as a general approach to van der Waals parameters on all types of hydrogens. © 1992 by John Wiley & Sons, Inc.