Chemogenomics knowledgebase and systems pharmacology for hallucinogen target identification-Salvinorin A as a case study.
Drug abuse is a serious problem worldwide. Recently, hallucinogens have been reported as a potential preventative and auxiliary therapy for substance abuse. However, the use of hallucinogens as a drug abuse treatment has potential risks, as the fundamental mechanisms of hallucinogens are not clear. So far, no scientific database is available for the mechanism research of hallucinogens. We constructed a hallucinogen-specific chemogenomics database by collecting chemicals, protein targets and pathways closely related to hallucinogens. This information, together with our established computational chemogenomics tools, such as TargetHunter and HTDocking, provided a one-step solution for the mechanism study of hallucinogens. We chose salvinorin A, a potent hallucinogen extracted from the plant Salvia divinorum, as an example to demonstrate the usability of our platform. With the help of HTDocking program, we predicted four novel targets for salvinorin A, including muscarinic acetylcholine receptor 2, cannabinoid receptor 1, cannabinoid receptor 2 and dopamine receptor 2. We looked into the interactions between salvinorin A and the predicted targets. The binding modes, pose and docking scores indicate that salvinorin A may interact with some of these predicted targets. Overall, our database enriched the information of systems pharmacological analysis, target identification and drug discovery for hallucinogens.
Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Xiaomeng
X
Xu
Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Shifan
S
Ma
Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Zhiwei
Z
Feng
Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Guanxing
G
Hu
Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address: liw30@pitt.edu.
Lirong
L
Wang
Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA; NIDA National Center of Excellence for Computational Drug Abuse Research, University of Pittsburgh, Pittsburgh, PA 15261, USA; Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA; Departments of Computational Biology and of Structural Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address: xix15@pitt.edu.
Xiang-Qun
XQ
Xie
D062126:Databases, Chemical; D045785:Diterpenes, Clerodane / Q000737:chemistry / Q000494:pharmacology*; D023281:Genomics; D006213:Hallucinogens / Q000737:chemistry / Q000494:pharmacology*; D051188:Knowledge Bases; D008958:Models, Molecular; D015203:Reproducibility of Results
D045785:Diterpenes, Clerodane; D006213:Hallucinogens; C090499:salvinorin A
Chemogenomics database; Drug abuse; Hallucinogen; Salvinorin A; Systems pharmacology; Target identification