Monte Carlo docking procedure

Caflisch et al. demonstrated that a two-step procedure incorporating a Monte Carlo minimization procedure can dock flexible oligopeptides to static proteins. Step one involves rigid rotations and translations of a preselected conformation. Step two involves taking the low energy conformation(s) produced in step one and carrying out 400 cycles of Monte Carlo minimization. The bound conformation of the HIV protease inhibitor MVT-101 was well reproduced by the method. 

However, it is normally assumed that the conformers that bind to target sites will be those with a minimum potential energy. Since molecules may have large numbers of such metastable conformers a number of techniques, such as the Metropolis Monte Carlo method and comparative molecular field analysis (CoMFA), have been developed to determine the effect of conformational changes on the effectiveness of docking procedures. 

The Monte Carlo calculations were performed by means of BIOSYMs Solids Docking program and the DISCOVER molecular mechanics calculations. The procedure starts with a high temperature molecular dynamics simulation of the guest molecule in vacuo. 

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