AUTOMATED STRUCTURAL REFINEMENT OF DOCKED COMPLEXES IN CYTOCHROME P450 USING MOLECULAR DYNAMICS

Docking and molecular dynamics are commonly used methods in drug development for the prediction of interactions between the drug in question and the target protein. When used together, docking studies can provide starting structures for molecular dynamics, which can improve the relatively low accuracy of docking but at greater computational cost. When the structure contains a cofactor with covalently bound metal atom, few automated methods are capable of setting up the system to perform molecular dynamics simulations. Another limitation that can be encountered is the parametrization of the ligand, which is not always easy to set up and automate using popular suites, such as AMBER or GROMACS. Here, we propose an automated workflow for setting up and running the simulation, providing a seamless integration for both flexible and rigid protein docking engines. The automatic setup works for around 90\% of all ligands for rigid docking engines, with this number decreasing for RoseTTAFold All-Atom (flexible docking engine) to around 30\% due to its known problem with hallucination of the ligand conformation.