Molecular modeling suite 2019

The crystal structures of ATX (PDB ID: 3NKM) and LPAR1 (PDB ID: 4Z35) were obtained from Protein Data Bank. The ligand structures were built and prepared by using the LigPrep tool of modeling software Schrödinger Molecular Modeling Suite 2019 (Schrödinger LLC, New York, NY). The proteins were preprocessed by adding hydrogens, filling the missing chains, optimizing hydrogen bonds, and minimizing energy using Protein Preparation Wizard workflow with procedures similar to those described before. 51 The receptor grid of 3NKM was generated by centering the binding site enclosing box on the major residues at the active binding site, including Lys39, Arg124, and Glu293, using the Receptor Grid Generation. The receptor grid of LPAR1 was generated with a grid box centered on the active ligand-binding site. Then the standard precision of flexible molecular docking was performed by using the Glide Docking module. The binding modes of the ligands and data analysis were carried out using Maestro. The glide docking score generated in the docking represents an estimated binding energy when a ligand binds to the receptor. A lower ligand glide docking score normally demonstrates a more favorable binding interaction with the receptor.