A Combined Computational and Experimental Approach for Structure Prediction of Foldamers

在化学部大分子、超分子和纳米化学（MSN）项目的支持下，费城科学大学（USP）化学和生物化学系的Vojislava Pophristic博士和Guillermo Moyna博士以及费尔利·迪金森大学（FDU）化学和药物科学系的Alexey Teslja博士将开发一种方法来增强文件夹的合理设计。折叠物是一种合成的低聚物，在溶液中具有明确的、稳定的二级结构，在许多不同的科学领域有许多已经实现和潜在的应用。该方案的主要目标是在文件夹构建块和最终文件夹结构之间建立信息可传递性。该研究将重点关注一类重要的折叠物——芳基酰胺类，它的主干具有[-（芳香环-肽单元）n-]模式，其构象偏好显著取决于芳香环取代基的特定性质和位置，以及环境。利用计算化学方法、合成、核磁共振和红外光谱的结合，研究人员将研究二聚体到十二聚体在各种溶剂中的构象和能量学。这项工作将导致建立一个数据库，其最终目标是快速准确地预测芳酰胺折叠构象。研究还将得出合适的力场参数，并勾勒出提高文件夹合理设计的总体策略。这项研究的潜在影响是提高了建模的能力，从而设计出具有新颖应用的新文件夹。研究结果和数据将通过同行评议的出版物和科学会议上的报告以及通过一个可公开访问的数据库提供。基于拟议研究提供的信息的一般性质，以及它对文件夹特定研究的适用性，预计广泛的科学界，如化学家、生物化学家和材料科学家，以及研究特定文件夹主题的研究人员，将从这项研究中非常积极地受益。该项目的外联计划涉及非博士FDU。资助机构，以促进和促进其化学研究计划的发展。USP和FDU的本科生和研究生将接受一系列技能的培训，包括计算化学、合成、核磁共振和红外光谱，以及如何有效地使用它们。

With the support of this award from the Macromolecular, Supramolecular, and Nanochemistry (MSN) program of the Chemistry Division, Dr. Vojislava Pophristic and Dr. Guillermo Moyna, of the Department of Chemistry and Biochemistry at the University of Sciences in Philadelphia (USP), and Dr. Alexey Teslja, of the Department of Chemistry and Pharmaceutical Science at the Fairleigh Dickinson University (FDU), will develop an approach to enhance rational design of foldamers. Foldamers are synthetic oligomers that adopt defined, stable secondary structures in solution, and have many realized and potential applications in a number of different scientific areas. The main objective of this proposal is to establish information transferability between the foldamer building blocks and the final foldamer structure. The research will focus on an important class of foldamers, the arylamide class, which features a backbone with a [-(aromatic ring-peptide unit)n-] pattern whose conformational preference significantly depends on specific nature and location of aromatic ring substituents, as well as the environment. Utilizing a combination of computational chemistry methods, synthesis, NMR and IR spectroscopy, the researchers will study the conformation and energetics of dimer to dodecamer units of the arylamide class in various solvents. The effort will lead to building a databank with the ultimate goal of rapid and accurate prediction of arylamide foldamer conformations. The research will also generate appropriate force field parameters and outline a general strategy to enhance rational design of foldamers. The potential impact of this research is in an increased ability to model, and thus design new foldamers, with novel applications. The results and data will be made available through peer reviewed publications and presentations at scientific meetings, as well as through a publicly accessible databank. Based on the general nature of the information to be provided by the proposed research, as well as its applicability to foldamer specific research, it is expected that both the broad scientific community, e.g. chemists, biochemists, and material scientists, as well as researchers working on specific foldamer topics, will benefit from this research very positively. The outreach plans of this project involve FDU, a non-Ph.D. granting institution, to promote and facilitate development of their research program in chemistry. Undergraduate and graduate students at both USP and FDU will be trained on a number of skill sets including computational chemistry, synthesis, NMR and IR spectroscopy, as well as on how to use them together efficiently.