Chemogenomics knowledgebase and systems pharmacology for hallucinogen target identification-Salvinorin A as a case study.

A new chemogenomics database specific to hallucinogens was built by collecting related chemicals, protein targets, and pathways. Combined with computational tools TargetHunter and HTDocking, it offers a one-step platform for studying hallucinogen mechanisms. Using salvinorin A from Salvia divinorum as a test case, HTDocking predicted four novel targets: muscarinic acetylcholine receptor 2, cannabinoid receptors 1 and 2, and dopamine receptor 2. Binding modes, poses, and docking scores suggest salvinorin A may interact with some of these targets. The database enriches systems pharmacology analysis, target identification, and drug discovery for hallucinogens, addressing the lack of a dedicated resource for mechanism research.

Study at a glance

Abstract

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.