BioDrugScreen: a computational drug design resource for ranking molecules docked to the human proteome

Abstract

BioDrugScreen is a resource for ranking molecules docked against a large number of targets in the human proteome. Nearly 1600 molecules from the freely available NCI diversity set were docked onto 1926 cavities identified on 1589 human targets resulting in >3 million receptor–ligand complexes requiring >200 000 cpu-hours on the TeraGrid. The targets in BioDrugScreen originated from Human Cancer Protein Interaction Network, which we have updated, as well as the Human Druggable Proteome, which we have created for the purpose of this effort. This makes the BioDrugScreen resource highly valuable in drug discovery. The receptor–ligand complexes within the database can be ranked using standard and well-established scoring functions like AutoDock, DockScore, ChemScore, X-Score, GoldScore, DFIRE and PMF. In addition, we have scored the complexes with more intensive GBSA and PBSA approaches requiring an additional 120 000 cpu-hours on the TeraGrid. We constructed a simple interface to enable users to view top-ranking molecules and access purchasing and other information for further experimental exploration.

Virtual screening: An in silico tool for interlacing the chemical universe with the proteome

“…In comparison with VS, IVS is computationally more demanding because each protein's binding site needs to be defined and protein files are usually larger than ligand files, demanding considerable processing speed, random access memory, and disk storage space. Examples of databases suitable for automated docking are: sc-PDB, PDTD [172], Anonymous [155], BioDrugScreen [203], SePreSa [204] and DAR-CPI [205]. It is also well known that the quality of protein structures may decrease from experimental structures to homology models [206], and this should be considered when including structures fitting into a particular biological context of interest into target databases.…”

An Overview of Computational Life Science Databases & Exchange Formats of Relevance to Chemical Biology Research

“…(www.biodrugscreen.org) [27] is a combined web-based drug discovery database and analysis server. The database portion of the service consists of the Docked Proteome Interaction Network (DOPIN).…”

A history of the TeraGrid science gateway program

“…BioDrugScreen [43]. (Meroueh) This gateway ( Figure 6) provides data and scoring function tools for both pre-docked and ondemand docking of drug-like molecules with protein targets from the Protein Data Bank.…”