DAKB-GPCRs: An Integrated Computational Platform for Drug Abuse Related GPCRs

J Chem Inf Model. 2019 Apr 22;59(4):1283-1289. doi: 10.1021/acs.jcim.8b00623. Epub 2019 Mar 14.


Drug abuse (DA) or drug addiction is a complicated brain disorder which is commonly considered as neurobiological impairments caused by both genetic factors and environmental effects. Among DA-related targets, G protein-coupled receptors (GPCRs) play an important role in DA therapy. However, only 52 GPCRs have been published with crystal structures in the recent two decades. In the effort to overcome the limitations of crystal structure and conformational diversity of GPCRs, we built homology models and performed conformational searches by molecular dynamics (MD) simulation. To accelerate and facilitate the drug abuse research, we construct a DA-related GPCR-specific chemogenomics knowledgebase (KB) (DAKB-GPCRs) for its research that can be implemented with our established and novel chemogenomics tools as well as algorithms for data analysis and visualization. Our established TargetHunter and HTDocking tools, as well as our novel tools that include target classification and Spider Plot, are compiled into the platform. Our DAKB-GPCRs provides the following results for a query compound: (1) blood-brain barrier (BBB) plot via our BBB predictor, (2) docking scores via HTDocking, (3) similarity score via TargetHunter, (4) target classification via machine learning methods that utilize both docking scores and similarity scores, and (5) a drug-target interaction network via Spider Plot.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Computational Biology / methods*
  • Knowledge Bases
  • Molecular Docking Simulation
  • Molecular Targeted Therapy
  • Protein Conformation
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Substance-Related Disorders / drug therapy*
  • Substance-Related Disorders / metabolism*


  • Receptors, G-Protein-Coupled