Departments of Biological Sciences, Chemistry, Bioengineering, and Computer Science and Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, United States.
J Chem Inf Model. 2021 Nov 22;61(11):5336-5342. doi: 10.1021/acs.jcim.1c01156. Epub 2021 Nov 10.
Rational drug design involves a task of finding ligands that would bind to a specific target protein. This work presents CHARMM-GUI that is an intuitive and interactive web-based tool to design virtual ligands that match the shape and chemical features of a given protein binding site. provides ligand modification capabilities with 3D visualization that allow researchers to modify and redesign virtual ligands while viewing how the protein-ligand interactions are affected. Virtual ligands can also be parameterized for further molecular dynamics (MD) simulations and free energy calculations. Using 8 targets from 8 different protein classes in the directory of useful decoys, enhanced (DUD-E) data set, we show that can produce similar ligands to the known active ligands in the crystal structures. also produces stable protein-ligand complex structures when tested using short MD simulations. We expect that can be a useful and user-friendly tool to design small molecules in any given potential ligand binding site on a protein of interest.
理性药物设计涉及寻找与特定靶标蛋白结合的配体的任务。本工作介绍了 CHARMM-GUI，这是一个直观的、基于网络的工具，用于设计与给定蛋白质结合位点的形状和化学特征相匹配的虚拟配体。它提供了带有 3D 可视化的配体修饰功能，允许研究人员在观察蛋白质-配体相互作用如何受到影响的同时，对虚拟配体进行修改和重新设计。虚拟配体还可以进行参数化，以进行进一步的分子动力学 (MD) 模拟和自由能计算。使用有用的诱饵目录中的 8 个来自 8 个不同蛋白质类别的靶标，增强 (DUD-E) 数据集，我们表明可以生成与晶体结构中已知活性配体相似的配体。还可以通过使用短 MD 模拟进行测试，生成稳定的蛋白质-配体复合物结构。我们预计 CHARMM-GUI 可以成为在感兴趣的蛋白质上的任何给定潜在配体结合位点设计小分子的有用和用户友好的工具。
