Rome Center for Molecular Design, Dipartimento di Chimica e Tecnologie del Farmaco, Facoltà di Farmacia e Medicina, Sapienza Università di Roma, P.le A. Moro 5, 00185 Rome, Italy.
J Chem Inf Model. 2012 Aug 27;52(8):2215-35. doi: 10.1021/ci300160y. Epub 2012 Jul 19.
An enhanced version of comparative binding energy (COMBINE) analysis, named COMBINEr, based on both ligand-based and structure-based alignments has been used to build several 3-D QSAR models for the eleven human zinc-based histone deacetylases (HDACs). When faced with an abundance of data from diverse structure-activity sources, choosing the best paradigm for an integrative analysis is difficult. A common example from studies on enzyme-inhibitors is the abundance of crystal structures characterized by diverse ligands complexed with different enzyme isoforms. A novel comprehensive tool for data mining on such inhomogeneous set of structure-activity data was developed based on the original approach of Ortiz, Gago, and Wade, and applied to predict HDAC inhibitors' isoform selectivity. The COMBINEr approach (apart from the AMBER programs) has been developed to use only software freely available to academics.
基于配体和结构比对的比较结合能（COMBINE）分析的增强版本，命名为 COMBINEr，已被用于构建十一种人类锌基组蛋白去乙酰化酶（HDACs）的多个三维定量构效关系（3-D QSAR）模型。当面对来自不同结构-活性来源的大量数据时，选择用于综合分析的最佳范例是困难的。酶抑制剂研究中的一个常见例子是存在大量晶体结构，这些结构由不同的配体与不同的酶同工型复合而成。基于 Ortiz、Gago 和 Wade 的原始方法，开发了一种用于此类非同质结构-活性数据的数据挖掘的新型综合工具，并将其应用于预测 HDAC 抑制剂的同工型选择性。COMBINEr 方法（除了 AMBER 程序外）是为仅使用学术人员可免费获得的软件而开发的。
