PrepFlow: A Toolkit for Chemical Library Preparation and Management for Virtual Screening

Abstract

In the era of big data in Chemistry, the need for automated tools for virtual screening is compelling. Here, we present PrepFlow a toolkit for chemical library preparation and management. Starting from a list of compounds in SMILES or 2D molecular format, PrepFlow outputs a set of 3D molecular structures ready for use in subsequent drug discovery projects. Our development stands out for speed and robustness of execution, the efficient exploitation of HPC resources, and the implementation of an archiving strategy to save computer time, storage, and human intervention. Using a random selection of 600 compounds from available drug banks, we show that the preparation time per ligand on a desktop computer is 6.6 s. Thanks to these performances and the automatic parallelization on HPC, a chemical library of the size of ChEMBL (2 M) was prepared in around 3 days on a computer cluster. PrepFlow is freely distributed at the following link: https://ifm.chimie.unistra.fr/prepflow.

ChemFlow─From 2D Chemical Libraries to Protein–Ligand Binding Free Energies

“…The resulting dataset is highly relevant for virtual screening purposes because (1) it features 626 protein–ligand complexes with drug-like organic compounds; (2) it includes 234 distinct proteins, 25 of which cocrystallized with ≥5 ligands; (3) it was curated by experts from the pharmaceutical industry; (4) it provides high-resolution structures (X-ray) and thermodynamic data (p K d ) for all complexes; and (5) it comes with in silico predictions for benchmarking computational methods (see Tables S6 and S7 for details). To emulate a typical vHTS campaign, the ligands were extracted and processed by PrepFlow . The chemical library was prepared using GAFF2 parameters and RESP charges and forwarded to DockFlow, which prioritized 10 binding modes per ligand via PLANTS and the ChemPLP scoring function .…”

“…To emulate a typical vHTS campaign, the ligands were extracted and processed by PrepFlow. 27 The chemical library was prepared using GAFF2 parameters and RESP charges and forwarded to DockFlow, which prioritized 10 binding modes per ligand via PLANTS and the ChemPLP scoring function. 39 The best binding pose per ligand along with the coordinates of the protein were postprocessed by ScoreFlow.…”

“…ChemFlow is shipped with three independent modules: DockFlow, LigFlow, and ScoreFlow (Figure ). In coordination with the standalone software PrepFlow, which was designed to handle chemical library preparation robustly and efficiently, hundreds of thousands of ligands are prepared, docked, prioritized, and finally reranked using simplified free energy calculations by ChemFlow. Starting from the output of PrepFlow, DockFlow performs virtual high-throughput docking against one or multiple targets using four popular docking codes: AutoDock Vina, QVINA, SMINA, and PLANTS .…”

A Guide to In Silico Drug Design

“…Balloon [ 142 ], a free conformer generator, uses distance geometry to generate an initial conformer for a ligand, followed by a multi-objective genetic algorithm approach to modify torsion angles around rotatable bonds, stereochemistry of double bonds, chiral centres, and ring conformations. Some other tools that were developed for ligand preparation include Prepflow [ 144 ], VSPrep [ 145 ], Gypsum-DL [ 146 ], Frog2 [ 147 ] and UNICON [ 148 ].…”