Modulation of γ-aminobutyric acid (GABA) levels has been required in various disorders. GABA itself cannot be directly introduced into central nervous system (CNS) because of the blood brain barrier; inhibition of GABA aminotransferase (GABA-AT), which degrades GABA in CNS, has been the target for the modulation of GABA levels in CNS. Given that root extract of valerian (Valeriana officinalis) has been used for millennia as anti-anxiolytic and sedative, in silico approach was carried out to investigate valerian compounds exhibiting GABA-AT inhibiting activity. The 3D structure of human GABA-AT was created from pig crystal structure via homology modeling. Inhibition of GABA-AT by 18 valerian compounds was analyzed using molecular docking and molecular dynamics simulations and compared with known GABA-AT inhibitors such as vigabatrin and valproic acid. Isovaleric acid and didrovaltrate exhibited GABA-AT inhibiting activity in computational analysis, albeit less potent compared with vigabatrin. However, multiple compounds with low activity may have additive effects when the total extract of valeriana root was used in traditional usage. In addition, isovaleric acid shares similar backbone structure to GABA, suggesting that isovaleric acid might be a valuable starting structure for the development of more efficient GABA-AT inhibitors for disorders related with low level of GABA in the CNS.

中文翻译：

---

通过分子对接和分子动力学模拟研究，从缬草成分中筛选GABA氨基转移酶抑制剂。

在各种疾病中都需要调节γ-氨基丁酸（GABA）的水平。由于血脑屏障，GABA本身不能直接引入中枢神经系统（CNS）；抑制中枢神经系统中的GABA降解的GABA氨基转移酶（GABA-AT）已成为中枢神经系统中GABA水平调节的目标。鉴于缬草的根提取物（Valeriana officinalis）作为抗焦虑和镇静剂已被使用了数千年，采用计算机方法研究了具有GABA-AT抑制活性的缬草化合物。人类GABA-AT的3D结构是通过同源建模从猪的晶体结构创建的。使用分子对接和分子动力学模拟分析了18种缬草化合物对GABA-AT的抑制作用，并与已知的GABA-AT抑制剂（如vigabatrin和丙戊酸）进行了比较。异戊酸和去甲丙戊酸盐在计算分析中表现出GABA-AT抑制活性，尽管与vigabatrin相比效力较低。但是，当缬草根的总提取物用于传统用途时，多种低活性化合物可能具有加和作用。此外，异戊酸与GABA具有相似的骨架结构，