Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
J Mol Biol. 2022 Jun 15;434(11):167587. doi: 10.1016/j.jmb.2022.167587. Epub 2022 Apr 18.
Protein mapping distributes many copies of different molecular probes on the surface of a target protein in order to determine binding hot spots, regions that are highly preferable for ligand binding. While mapping of X-ray structures by the FTMap server is inherently static, this limitation can be overcome by the simultaneous analysis of multiple structures of the protein. FTMove is an automated web server that implements this approach. From the input of a target protein, by PDB code, the server identifies all structures of the protein available in the PDB, runs mapping on them, and combines the results to form binding hot spots and binding sites. The user may also upload their own protein structures, bypassing the PDB search for similar structures. Output of the server consists of the consensus binding sites and the individual mapping results for each structure - including the number of probes located in each binding site, for each structure. This level of detail allows the users to investigate how the strength of a binding site relates to the protein conformation, other binding sites, and the presence of ligands or mutations. In addition, the structures are clustered on the basis of their binding properties. The use of FTMove is demonstrated by application to 22 proteins with known allosteric binding sites; the orthosteric and allosteric binding sites were identified in all but one case, and the sites were typically ranked among the top five. The FTMove server is publicly available at https://ftmove.bu.edu.
蛋白质绘图技术通过在目标蛋白质的表面分布许多不同的分子探针，以确定结合热点，即配体结合高度优选的区域。虽然 FTMap 服务器对 X 射线结构的映射本质上是静态的，但通过同时分析蛋白质的多个结构可以克服这一限制。FTMove 是一个自动化的网络服务器，实现了这种方法。从目标蛋白质的输入，通过 PDB 代码，服务器识别 PDB 中可用的该蛋白质的所有结构，对它们进行映射，并将结果组合起来形成结合热点和结合部位。用户也可以上传自己的蛋白质结构，绕过 PDB 搜索类似的结构。服务器的输出包括共识结合部位和每个结构的单独映射结果 - 包括位于每个结合部位的探针数量，对于每个结构。这种详细程度允许用户研究结合部位的强度与蛋白质构象、其他结合部位以及配体或突变的存在之间的关系。此外，结构根据其结合特性进行聚类。FTMove 的使用通过应用于 22 个具有已知变构结合部位的蛋白质来证明；在所有情况下都确定了正位和变构结合部位，并且这些部位通常排在前五位。FTMove 服务器可在 https://ftmove.bu.edu 上公开获得。
