Searching The Conformational Space For Docking - Molecular Dynamics (MD) Simulations

Molecular Dynamics (MD) Simulations

In this approach, proteins are typically held rigid, and the ligand is allowed to freely explore their conformational space. The generated conformations are then docked successively into the protein, and an MD simulation consisting of a simulated annealing protocol is performed. This is usually supplemented with short MD energy minimization steps, and the energies determined from the MD runs are used for ranking the overall scoring. Although this is a computer-expensive method (involving potentially hundreds of MD runs), it has some advantages: for example, no specialized energy/scoring functions are required. MD force-fields can typically be used to find poses that are reasonable and can be compared with experimental structures.

The Distance Constrained Essential Dynamics method (DCED) has been used to generate multiple structures for docking, called eigenstructures. This approach, although avoiding most of the costly MD calculations, can capture the essential motions involved in a flexible receptor, representing a form of coarse-grained dynamics.