Molecular Dynamics Simulations Enhance Screening Accuracy for CSLs: A Desmond Module-Based Approach

To enhance screening accuracy, we utilized the MD simulation method as the CSLs were recently reported and had similar structures. The Desmond Module of the Schrödinger suite 2020-3, which runs on the Linux platform with a 12GB NVIDIA TELSA P100 graphics GPU, was employed. MD simulations were conducted for 100 nanoseconds (ns) to observe the stability of the complexes docked with ligands. The System Builder module and OPLS3E force field were utilized to construct the ensemble, while the TIP3P water model was used as the solvent model. Default parameters were recalculated, including the ion addition and salt addition (0.15 M KCl), to neutralize and stabilize the solution system. The canonical ensemble was used with isothermal and isobaric simulation (NPT) to ensure constant temperature and pressure. GPU processors were used to accelerate MD, and recordings were taken at every 10 ps at a temperature of 310 K and pressure of 1 atmosphere. The post-MD simulation analysis was conducted using the Maestro-Desmond interoperability tools, and various parameters such as RMSD, Protein Root Mean Square Fluctuation (RMSF), Ligand RMSF, Protein-Ligand interaction, Ligand torsion and Ligand properties were analyzed. Results were generated and analyzed in PDF format and exported to images.