Ropp Patrick J, Kaminsky Jesse C, Yablonski Sara, Durrant Jacob D
Department of Biological Sciences, University of Pittsburgh, 4249 Fifth Avenue, Pittsburgh, PA, 15260, USA.
J Cheminform. 2019 Feb 14;11(1):14. doi: 10.1186/s13321-019-0336-9.
Small-molecule protonation can promote or discourage protein binding by altering hydrogen-bond, electrostatic, and van-der-Waals interactions. To improve virtual-screen pose and affinity predictions, researchers must account for all major small-molecule ionization states. But existing programs for calculating these states have notable limitations such as high cost, restrictive licenses, slow execution times, and poor modularity. Here, we present dimorphite-DL 1.0, a fast, accurate, accessible, and modular open-source program for enumerating small-molecule ionization states. Dimorphite-DL uses a straightforward empirical algorithm that leverages substructure searching and draws on a database of experimentally characterized ionizable molecules. We have tested dimorphite-DL using several versions of Python and RDKit on all major operating systems. We release it under the terms of the Apache License, Version 2.0. A copy is available free of charge from http://durrantlab.com/dimorphite-dl/ .
小分子质子化可通过改变氢键、静电和范德华相互作用来促进或抑制蛋白质结合。为了改进虚拟筛选构象和亲和力预测，研究人员必须考虑所有主要的小分子电离状态。但是，现有的计算这些状态的程序存在显著局限性，如成本高、许可证限制、执行时间长和模块化差等问题。在此，我们展示了Dimorphite-DL 1.0，这是一个用于枚举小分子电离状态的快速、准确、可访问且模块化的开源程序。Dimorphite-DL使用一种简单的经验算法，该算法利用子结构搜索并借鉴了具有实验特征的可电离分子数据库。我们已在所有主流操作系统上使用多个版本的Python和RDKit对Dimorphite-DL进行了测试。我们根据Apache许可证2.0版的条款发布它。可从http://durrantlab.com/dimorphite-dl/免费获取一份副本。
