Flexible docking in solution using metadynamics.

Francesco Luigi Gervasio; Alessandro Laio; Michele Parrinello

doi:10.1021/ja0445950

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PubMed · 15725015

Flexible docking in solution using metadynamics.

Francesco Luigi Gervasio·Alessandro Laio·Michele Parrinello

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Abstract

We apply our recently developed metadynamics method to the docking of ligands on flexible receptors in water solution. This method mimics the real dynamics of a ligand exiting or entering an enzyme and in so doing reconstructs the free energy surface. We apply it to four docking cases: beta-trypsin/benzamidine, beta-trypsin/chlorobenzamidine, immunoglobulin McPC-603/phosphocholine, and cyclin-dependent kinase 2/staurosporine. In every case studied, the method is able to predict the docked geometry and the free energy of docking. Its added value with respect to many other available methods is that it reconstructs the complete free energy surface, including all the relevant minima and the barriers between them.

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Benzamidines CDC2-CDC28 Kinases Computer Simulation Cyclin-Dependent Kinase 2 Immunoglobulins Kinetics Ligands Models, Molecular Phosphorylcholine Staurosporine Thermodynamics Trypsin Journal Article

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Francesco Luigi Gervasio, Alessandro Laio, Michele Parrinello. 2005-03-02. Flexible docking in solution using metadynamics.. https://doi.org/10.1021/ja0445950

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