人体GABA (B)（γ-氨基丁酸）受体是一个G蛋白偶联受体，对大脑中的抑制性神经传递发挥重要作用。GABA (B) 受体的功能异常将导致很多神经系统疾病，包括痉挛、癫痫、慢性疼痛和药物依赖。结合解析的GABA (B) 受体与配体相互作用的结构信息，我们根据临床药物 (R)-Baclofen合理的设计了一系列化合物。另外，我们针对GABA (B) 受体与激动剂和拮抗剂的结合位点，以及激动剂结合诱导形成的一个新的结合界面，通过虚拟筛选发现了一些激动剂、拮抗剂和别构调节剂。我们将测定其活性，并通过共结晶的方法优化这些化合物。我们发现的这些化合物可能会作为治疗GABA (B) 受体相关疾病的潜在药物。

Human GABA(B) (γ-aminobutyric acid class B) receptor is a G protein-coupled receptor central to inhibitory neurotransmission in the brain. Malfunction of GABA (B) receptors has been implicated in various neurological disorders, including spasticity, epilepsy, chronic pain and drug abuse. Taking advantage of the detailed structural information we have gathered for GABA (B) receptors-ligand interactions, we will rationally design a series of novel agonists based on the clinical drug (R)-baclofen. We will also identify potential agonist, antagonist and allosteric modulator of the receptors by virtual screening against the agonist- and antagonist-binding sites as well as the heterodimer interface. We plan to synthesize new drug candidates based on these initial compounds, measure their functional effects, and determine co-crystal structures of GABA (B) receptors with these compounds. The novel compounds developed in our study may serve as drug candidates for the treatment of GABA (B)-associated diseases.