International Collaboration in Chemistry: Electron Delocalization in Polypeptide Structure and Stability

有了这个国际化学合作（ICC）奖，化学系的生命过程化学（CLP）计划支持罗纳德T教授的合作工作。威斯康星大学麦迪逊分校的雷恩斯和德里克N。Woolfson的布里斯托大学，进行蛋白质结构和稳定性的基础研究，着眼于了解二级轨道相互作用。 英国Woolfson实验室的研究得到了合作机构工程和物理科学研究理事会（EPSRC）的支持。 该奖项由NSF国际科学与工程办公室（OISE）共同资助。蛋白质结构和组装是由各种非共价相互作用指导，稳定和控制的。 最近，这个合作团队的工作表明，一种鲜为人知的力，基于n-to-pi* 相互作用，在蛋白质结构中广泛存在，并可能在稳定性和功能中发挥作用。 基于这一新发现，拟议的研究有两个总体目标：（1）利用生物信息学探测现有公共数据库（即剑桥结构数据库（CSD）和RCSB）的高分辨率多肽结构中的n到pi* 和类似相互作用（Brookhaven）蛋白质数据库（PDB）;和（2）使用化学来探索通过骨架化学修饰增强n-到-pi* 相互作用来稳定肽和蛋白质结构的可能性。结果可能包括更好地理解肽和蛋白质结构中的非共价力，以及稳定这些结构的一般方法。除了可能改变化学家对肽中构象和轨道相互作用的思考方式的科学广泛影响外，还有重要的教育广泛影响。这个NSF-EPSRC ICC奖将使参与的学生和博士后与合作实验室的同事一起体验国际合作研究的第一手资料。

With this International Collaboration in Chemistry (ICC) award, the Chemistry of Life Processes (CLP) program of the Division of Chemistry is supporting collaborative work by Professor Ronald T. Raines of the University of Wisconsin-Madison and Professor Derek N. Woolfson of the University of Bristol, to carry out fundamental studies on protein structure and stability, with an eye toward understanding secondary orbital interactions. Research in the Woolfson laboratory in the UK is supported by the partnering agency, the Engineering and Physical Sciences Research Council (EPSRC). This award is being co-funded by the NSF Office of International Science and Engineering (OISE).Protein structures and assemblies are directed, stabilized, and governed by a wide variety of non-covalent interactions. Recently, work from this collaborative team suggested that a lesser-known force, based upon n-to-pi* interactions, is widespread in protein structures, and likely plays roles in stability and function. Building on this new finding, the proposed research has two overarching objectives: (1) using bioinformatics to probe n-to-pi* and analogous interactions in high-resolution polypeptide structures of the available public databases, namely the Cambridge Structural Database (CSD) and the RCSB (Brookhaven) Protein Data Bank (PDB); and (2) using chemistry to explore the possibility of stabilizing peptide and protein structures by enhancing n-to-pi* interactions through backbone chemical modification. Outcomes could include a better understanding of non-covalent forces in peptide and protein structures, and a general means to stabilize those structures.In addition to scientific broader impacts in potentially changing the way chemists think about conformation and orbital interactions in peptides, there are significant educational broader impacts. This NSF-EPSRC ICC award will enable participating students and postdoctorates to experience international collaborative research first hand with colleagues in the partnering laboratory.