TOLEDO: enhancing Maestro GUI for non-expert users to perform massive MD simulations.

Classical Molecular Dynamics (MD) simulates the dynamical evolution of biological systems at the atomic level. Using MD in conjunction with high-performance computing (HPC) architectures, we can evaluate the possible interactions between a ligand library against one protein target to find a drug that can influence a protein target to cure a disease. Simultaneously, we can also obtain information about their dynamic evolution. One of the primary software packages for MD simulations is Desmond, which employs Maestro for the setup, execution, and analysis of MD through a graphical user interface (GUI), which is suitable even for non-expert users. However, using the GUI, users can typically run only one short (less than 1000 ns) MD each time. Our work aims to create a method/protocol to run several MD simulations simultaneously on a remote HPC cluster within Maestro-Desmond. In this work, we provide TOLEDO (Throughput Optimization of Ligand-Protein Systems Exploration through Dynamics simulation in Optimized HPC systems) to overcome such limitations and run several MD simulations simultaneously. The best feature of TOLEDO is its independence from the usual time constraints of many clusters, with storage space being the only limitation. To run TOLEDO, we prepare/set up the protein-ligand complex before running MD via Maestro GUI. Next, we run the main TOLEDO script for several MD simulations on a supercomputer. When TOLEDO finishes, users obtain reports and graphics. The obtained results are easily interpretable. In essence, TOLEDO significantly enhances MD throughput beyond the capabilities of the Maestro GUI.