Proteins are not rigid, they do not exist in a single native conformation, but in an ensemble of states with different energies. With the use of molecular dynamics approaches an ensemble of these conformational states can be generated to enhance the virtual screening process. This include dynamic pharmacophores where a pharmacophore model is created from MD trajectories, and the relaxed complex scheme that uses snapshots from MD simulations to search ligand libraries.
There are some challenges and difficulties associated with MD simulations such as the inclusion of water molecules interactions, the total time of the simulations, and the need for new methods to predict the binding free energy.
Amaro, Rommie, and Wilfred Li. “Emerging Methods for Ensemble-Based Virtual Screening.” Current Topics in Medicinal Chemistry 10, no. 1 (2010): 3–13.
Proteins are not rigid, they do not exist in a single native conformation, but in an ensemble of states with different energies. With the use of molecular dynamics approaches an ensemble of these conformational states can be generated to enhance the virtual screening process. This include dynamic pharmacophores where a pharmacophore model is created from MD trajectories, and the relaxed complex scheme that uses snapshots from MD simulations to search ligand libraries.
There are some challenges and difficulties associated with MD simulations such as the inclusion of water molecules interactions, the total time of the simulations, and the need for new methods to predict the binding free energy.