Mining Multiple Solvent Crystal Structures for Properties of Protein Binding Sites

蛋白质是一种生物聚合物，可以折叠成特定的三维结构。它们是生命的分子主力，参与各种各样的功能，如增加化学反应的速率，储存和运输小分子，如氧气，介导细胞内信号或“指令”的传播等等。大多数蛋白质的功能包括通过所谓的结合位点表面的特殊特征与小分子或另一种蛋白质结合。马托斯博士和她的团队成员对了解蛋白质结合位点与蛋白质表面其他区域的区别特征很感兴趣。这个项目的目的是通过观察各种小分子是如何结合到一组经过充分研究的蛋白质上的，使用一种叫做x射线晶体学的方法，这种方法可以在接近原子分辨率的情况下可视化蛋白质和相关小分子的三维结构。Mattos实验室已经收集了这类分析所需的实验数据集，现在正在使用计算方法来挖掘蛋白质表面基本特性的数据集，特别是结合位点。定量方法将用于验证在小分子溶剂环境中获得的蛋白质表面性质与在更自然的水环境中观察到的蛋白质表面性质之间的对应关系。一旦验证完成，基本的蛋白质结合位点性质将直接从在非天然溶剂环境中获得的实验数据集中获得。了解蛋白质结合位点的特性对于理解蛋白质如何工作至关重要，因此也是理解复杂生命过程的重要一步。更广泛的impactDr。Mattos以这样一种方式开发了这个项目，研究是本科生教学的一个组成部分。这项研究将建立在她已经在她的小组中创造的繁荣和多样化的教育环境之上。每年，她班上的10名本科生将被邀请与研究生和实验室更资深的成员一起工作。该团队将与英国欧洲生物信息学研究所（EBI）的Janet Thornton教授小组进行国际合作，该研究所在蛋白质实验数据库的计算分析方面处于领先地位。Mattos博士最近刚从EBI休假回来，在此期间，一名研究生和一名本科生也参加了研究。她计划继续让学生参与这一国际合作。此外，Mattos博士还参与指导美国多所大学的少数族裔初级教员，并致力于鼓励北卡罗莱纳州立大学的少数族裔本科生和研究生为研究生院的奖学金申请撰写研究提案。

Intellectual meritProteins are biological polymers that fold into specific three-dimensional structures. They are the molecular workhorses of life and are involved in a wide variety of functions such as increasing the rates of chemical reactions, storing and transporting small molecules such as oxygen, mediating the propagation of signals or "instructions" within the cell and much more. Most protein function involves binding to a small molecule or another protein through special features on the surface within so-called binding sites. Dr. Mattos and members of her group are interested in understanding the features that distinguish binding sites on proteins from other areas on the protein surface. This project aims to do this by observing how a variety of small molecules bind to a set of well-studied proteins using a method called X-ray crystallography that allows visualization of the three-dimensional structure of proteins and the associated small molecules at near atomic resolution. The Mattos lab has collected the experimental data sets necessary for this type of analysis and is now using computational methods to mine the data sets for fundamental properties of protein surfaces in general and binding sites in particular. The quantitative methods will be used to validate the correspondence between protein surface properties obtained in the small molecule solvent environment and those observed in the more natural aqueous environment. Once the validation is complete the fundamental protein binding site properties will be directly obtained from experimental data sets acquired in the non-natural solvent environment. Understanding the properties of protein binding sites is critical to understanding of how proteins work and therefore a very important step in making sense of the complicated processes of life.Broader impactDr. Mattos has developed this project in such a way that research is an integral part of teaching undergraduates. The research will build on the thriving and diverse educational environment that she has already created in her group. Ten undergraduates from her classes each year will be invited to work with graduate students and the more senior members of the laboratory. The team will participate in an international collaboration with Prof. Janet Thornton's group at the European Bioinformatics Institute (EBI) in England, which is at the forefront of computational analysis of protein experimental databases. Dr. Mattos has recently returned from a sabbatical at the EBI, during which both a graduate and an undergraduate student also participated. She plans to continue to engage students in this international collaboration. In addition, Dr. Mattos is involved in mentoring minority junior faculty members at various universities in the United States and is working to encourage minority undergraduate and graduate students at North Carolina State University to write research proposals for fellowship applications to graduate school.