Department of Chemistry, Graduate School of Science , Tohoku University , 6-3, Aoba, Aramaki , Aoba-ku, Sendai , Miyagi 980-8578 , Japan.
Department of Physics, Graduate School of Pure and Applied Sciences , University of Tsukuba , 1-1-1 Tennodai , Tsukuba , Ibaraki 305-8571 , Japan.
J Chem Inf Model. 2019 Jan 28;59(1):25-30. doi: 10.1021/acs.jcim.8b00649. Epub 2018 Dec 20.
In modern praxis, a knowledge-driven design of pharmaceutical compounds relies heavily on protein structure data. Nonetheless, quantification of the interaction between protein and ligand is of great importance in the theoretical evaluation of the ability of a pharmaceutical compound to comply with certain expectations. The FMO (fragment molecular orbital) method is handy in this regard. However, the physical complexity and the number of the interactions within a protein-ligand complex renders analysis of the results somewhat complicated. This situation prompted us to develop the 3D-visualization of interaction energies in protein (3D-VIEP) method; the toolkit AnalysisFMO, which should enable a more efficient and convenient workflow with FMO data generated by quantum-chemical packages such as GAMESS, PAICS, and ABINIT-MP. AnalysisFMO consists of two separate units, RbAnalysisFMO, and the PyMOL plugins. The former can extract interfragment interaction energies (IFIEs) or pair interaction energies (PIEs) from the FMO output files generated by the aforementioned quantum-chemical packages. The PyMOL plugins enable visualization of IFIEs or PIEs in the protein structure in PyMOL. We demonstrate the use of this tool on a lectin protein from Burkholderia cenocepacia in which FMO analysis revealed the existence of a new interaction between Gly84 and fucose. Moreover, we found that second-shell interactions are crucial in forming the sugar binding site. In the case of bilirubin oxidase from Myrothecium verrucaria (MvBO), we predict that interactions between Asp105 and three His residues (His401, His403, and His136) are essential for optimally positioning the His residues to coordinate Cu atoms to form one Type 2 and two Type 3 Cu ions.
在现代实践中，药物化合物的知识驱动设计在很大程度上依赖于蛋白质结构数据。然而，在理论上评估药物化合物是否符合某些预期时，定量研究蛋白质与配体之间的相互作用非常重要。FMO（片段分子轨道）方法在此方面非常有用。然而，由于蛋白质-配体复合物内的物理复杂性和相互作用数量，分析结果有些复杂。这种情况促使我们开发了蛋白质相互作用能量的 3D 可视化（3D-VIEP）方法；AnalysisFMO 工具包，它应该能够使 FMO 数据的生成和分析更加高效和方便，这些数据是由 GAMESS、PAICS 和 ABINIT-MP 等量子化学软件包生成的。AnalysisFMO 由两个独立的单元组成，RbAnalysisFMO 和 PyMOL 插件。前者可以从上述量子化学软件包生成的 FMO 输出文件中提取片段间相互作用能（IFIE）或对相互作用能（PIE）。PyMOL 插件可以在 PyMOL 中可视化蛋白质结构中的 IFIE 或 PIE。我们在伯克霍尔德氏菌属假单胞菌的凝集素蛋白上展示了该工具的使用，在该蛋白中，FMO 分析揭示了 Gly84 与岩藻糖之间存在新的相互作用。此外，我们发现第二层相互作用对于形成糖结合位点至关重要。对于来自粘帚霉（Myrothecium verrucaria）的胆红素氧化酶（MvBO），我们预测 Asp105 与三个 His 残基（His401、His403 和 His136）之间的相互作用对于最佳定位 His 残基以协调 Cu 原子形成一个 Type 2 和两个 Type 3 Cu 离子至关重要。
