Pocket v.2: Further developments on receptor-based pharmacophore modeling
Pocket v.2: Further developments on receptor-based pharmacophore modeling
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DOI：
10.1021/ci600246s
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发表时间：
2006-11-27
影响因子：
5.6
通讯作者：
Lai, Luhua
中科院分区：
文献类型：
--
作者：
Chen, Jing;Lai, Luhua
从靶蛋白的三维结构推导药效团模型为分析蛋白质与配体的相互作用和进一步提高配体的结合亲和力提供了有用的信息。一个独立的程序，Pocket v.2，是基于新药设计程序LigBuilder中原始的Pocket模块开发的。Pocket v.2能够直接从给定的蛋白质-配体复合物结构中导出药效团模型，而无需人工干预。药效团模型中的关键特征自动减少到合理的数量。Pocket v.2已应用于几个案例研究，包括周期蛋白依赖性激酶2、HIV-1蛋白酶、雌激素受体和17 β -羟基类固醇脱氢酶。在所有这些情况下，它很好地复制了先前发表的药效团模型。Pocket v.2的一个显著特点是，它可以容忍不同配体结合后蛋白质侧的微小构象变化，从而提供一致的药效团模型。对于容纳相同配体的不同蛋白质，Pocket v.2给出了相似的药效团模型，这为根据结合特征对蛋白质进行分类提供了可能。
A deriving pharmacophore model from the three-dimensional structure of a target protein provides helpful information for analyzing protein-ligand interactions and further improvement of ligand binding affinity. A standalone program, Pocket v.2, has been developed based on the original Pocket module in the de novo drug design program LigBuilder. Pocket v.2 is able to derive a pharmacophore model directly from a given protein-ligand complex structure without human intervention. Key features in the pharmacophore model are automatically reduced to a reasonable number. Pocket v.2 has been applied to several case studies, including cyclin dependent kinase 2, HIV-1 protease, estrogen receptor, and 17 beta-hydroxysteroid dehydrogenase. It well reproduced previously published pharmacophore models in all of these cases. One notable feature of Pocket v.2 is that it can tolerate minor conformational changes on the protein side upon binding of different ligands to give a consistent pharmacophore model. For different proteins accommodating the same ligand, Pocket v.2 gives similar pharmacophore models, which opens the possibility to classify proteins with their binding features.