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）计划的支持下，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Fairleigh Dickinson大学（FDU）化学和药物科学系的Alexey Teslja博士，将开发一种方法，以提高合理设计的foldamer。折叠体是在溶液中采用确定的、稳定的二级结构的合成低聚物，并且在许多不同的科学领域中具有许多已实现的和潜在的应用。该提议的主要目的是建立折叠体构建块和最终折叠体结构之间的信息可传递性。该研究将集中在一类重要的折叠体，芳基酰胺类，其特征在于具有[-（芳环肽单元）n-]模式的骨架，其构象偏好显着取决于芳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，NMR和IR光谱的组合，研究人员将研究各种溶剂中芳基酰胺类的二聚体到十二聚体单元的构象和能量学。这项工作将导致建立一个数据库的最终目标是快速，准确地预测芳酰胺折叠体的构象。该研究还将产生适当的力场参数，并概述了一个总体战略，以提高合理的设计折叠机。这项研究的潜在影响是提高建模能力，从而设计具有新应用的新折叠体。结果和数据将通过同行评审的出版物和在科学会议上的介绍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，以及其对折叠分子特定研究的适用性，预计广泛的科学界，例如化学家、生物化学家和材料科学家，以及从事特定工作的研究人员。折叠分子主题，将从这项研究中非常积极地受益。该项目的推广计划涉及FDU，一个非博士学位。授予机构，以促进和促进化学研究计划的发展。USP和FDU的本科生和研究生将接受包括计算化学、合成、NMR和IR光谱在内的一系列技能培训，以及如何有效地将它们结合起来使用。

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.