Optimization and analysis of force field parameters by combination of genetic algorithms and neural networks

In search of a force field description for tripod metal templates, w Ž .Ž .Ž . x tripodM tripod s RC CH X CH Y CH Z ; X, Y, Z s PR9R0 force field 2 2 2 Ž . parameters, p, were optimized by the use of genetic algorithms GA with the Ž . structures of ten compounds, tripodMo CO , serving as the database. It was 3 found that the evaluation of the fitness criterion, based on the root-mean-square Ž . deviation rms between observed and calculated structures by force field methods, is actually the time-consuming step under this optimization protocol. It is shown now how this time-consuming step may in part be substituted by Ž . using a trained neural network NN as the evaluating function. The network is trained on the basis of parameter vectors that have been evaluated previously with respect to their corresponding rms values during several preceding Ž . generations of a GA run. The network function, rms s f p , thus built up is able to calculate the rms corresponding to a specific parameter vector within milliseconds, whereas obtaining the same result by molecular mechanics methods takes several minutes for the problem at hand and with the equipment used. Therefore, significant time savings may be expected using a combination of GA optimization and NN simulation In addition, the simulated function, Ž . rms s f p , allows for insights into the dependence of the rms value on specific parameters or combinations thereof. Kohonen mapping is used as a tool to visualize such dependence. Q 1999 John Wiley & Sons, Inc. J Comput Chem 20: 455]471, 1999