DrugRep: an automatic virtual screening server for drug repurposing

Abstract

Computationally identifying new targets for existing drugs has drawn much attention in drug repurposing due to its advantages over de novo drugs, including low risk, low costs, and rapid pace. To facilitate the drug repurposing computation, we constructed an automated and parameter-free virtual screening server, namely DrugRep, which performed molecular 3D structure construction, binding pocket prediction, docking, similarity comparison and binding affinity screening in a fully automatic manner. DrugRep repurposed drugs not only by receptor-based screening but also by ligand-based screening. The former automatically detected possible binding pockets of the receptor with our cavity detection approach, and then performed batch docking over drugs with a widespread docking program, AutoDock Vina. The latter explored drugs using seven well-established similarity measuring tools, including our recently developed ligand-similarity-based methods LigMate and FitDock. DrugRep utilized easy-to-use graphic interfaces for the user operation, and offered interactive predictions with state-of-the-art accuracy. We expect that this freely available online drug repurposing tool could be beneficial to the drug discovery community. The web site is http://cao.labshare.cn/drugrep/ .

Molecular Docking and Dynamics Simulation revealed the Potential Inhibitory Activity of Piomozide against Kynurenine metabolism targeting the Kynurenine 3-monooxygenase

“…Utilizing the DrugRep virtual screening server for high-throughput docking of KMO with FDA-approved, experimental, and traditional Chinese medicine libraries by the strategy of Receptor-based Screening (RBS) and drug repurposing (Gan et al 2023). RBS applies a novel cavity detection approach to automatically search the possible binding pockets and the results are shown interactively in a 3D viewer for users to select (Gan et al 2023). RBS also utilizes the co-crystallized ligand from PDB bind or useruploaded ligand to calculate the center and sizes of the docking box using AutoDock Tools and eBoxSize.…”

“…DrugRep provides three different collections of drugs, which include a library of FDA-approved drugs consisting of 2,315 drugs, a library of experimental drugs consisting of 5,935 drugs, and a traditional Chinese medicine library containing 2,390 drugs. FDA-approved and experimental drugs are from the DrugBank database (version 5.1.7) (Gan et al 2023). The drugs having higher docking scoresfrom the FDA-approved, experimental, and traditional Chinese medicine librarieswere selected for the molecular dynamic stimulation.…”

“…performs large-scale RBS based on CurPocket and AutoDock Vina making it accurate and convenient to prepare docking parameters(Gan et al 2023). Kynurenine 3-monooxygenase (KMO) is a avin adenine dinucleotide (FAD)-dependent monooxygenase enzyme that has a tightly bound FAD) cofactor(Hughes et al 2022).…”

Viral proteases as therapeutic targets

“…Computer aided design speeds up drug development, reduces experimental work and makes processes more cost-effective. Approaches, such as structure-based and ligand-based virtual screening, help to identify novel drugs, to optimize leading compounds ( da Silva Rocha et al, 2019 ; Evenseth et al, 2020 ; Proia et al, 2022 ) or can help in drug-repurposing strategies ( Gan et al, 2022 ; Mody et al, 2021 ). Positive hits identified, must be verified experimentally.…”

Drug screening against F13 protein, the target of tecovirimat, as potential therapies for monkeypox virus

“…We used DrugRep [7] , an AutoDock Vina-based online virtual screening server, to screen 10,640 compounds (workflow showed in fig. 1 a), containing 3 libraries: FDA-approved drugs (N=2,315), experimental drugs (N=5,935), and traditional Chinese medicine (TCM) monomer compounds (N=2,390).…”