Computer simulation receptor/ligand studies

Lopez-Rodriguez, M.L., Morcillo, M.J., Fernandez, E., Rosado, M.L., Pardo, L. and Schaper, K.-f. (2001) Synthesis and structure-activity relationships of a new model of arylpiperazines. 6. Study of the 5-HTiA/ai-adrenergic receptor affinity by classical Hansch analysis, artificial neural networks, and computational simulation of ligand recognition. Journal of Medicinal Chemistry, 44, 198-207. 

As an example for an efficient yet quite accurate approximation, in the first part of our contribution we describe a combination of a structure adapted multipole method with a multiple time step scheme (FAMUSAMM — fast multistep structure adapted multipole method) and evaluate its performance. In the second part we present, as a recent application of this method, an MD study of a ligand-receptor unbinding process enforced by single molecule atomic force microscopy. Through comparison of computed unbinding forces with experimental data we evaluate the quality of the simulations. The third part sketches, as a perspective, one way to drastically extend accessible time scales if one restricts oneself to the study of conformational transitions, which arc ubiquitous in proteins and are the elementary steps of many functional conformational motions. 

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