Virtual Ligand Screening Using PL-PatchSurfer2, a Molecular Surface-Based Protein–Ligand Docking Method
Virtual screening is a computational technique for predicting a potent binding compound for a receptor protein from a ligand library. It has been a widely used in the drug discovery field to reduce the efforts of medicinal chemists to find hit compounds by experiments.
Here, we introduce our novel structure-based virtual screening program, PL-PatchSurfer, which uses molecular surface representation with the three-dimensional Zernike descriptors, which is an effective mathematical representation for identifying physicochemical complementarities between local surfaces of a target protein and a ligand. The advantage of the surface-patch description is its tolerance on a receptor and compound structure variation. PL-PatchSurfer2 achieves higher accuracy on apo form and computationally modeled receptor structures than conventional structure-based virtual screening programs. Thus, PL-PatchSurfer2 opens up an opportunity for targets that do not have their crystal structures. The program is provided as a stand-alone program at http://kiharalab.org/plps2. We also provide files for two ligand libraries, ChEMBL and ZINC Drug-like.
Key wordsDrug discovery Molecular surface Protein–ligand interaction Three-dimensional Zernike descriptor Virtual screening 3DZD
We acknowledge Dan K. Ntala for proofreading the manuscript. This work was partly supported by grants from the National Science Foundation (IIS1319551). D.K. also acknowledges supports from National Institutes of Health (R01GM097528, R01GM123055) and the National Science Foundation (IOS1127027, DMS1614777).
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