A Combined Computational and Experimental Approach for Structure Prediction of Foldamers

在化学部高分子、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，将开发一种增强折叠剂合理设计的方法。Foldamer是一种在溶液中采用固定稳定的二级结构的合成低聚物，在许多不同的科学领域有许多已实现的和潜在的应用。这项提议的主要目标是在折叠式积木和最终折叠式结构之间建立信息可转移性。这项研究将集中在一类重要的芳酰胺类化合物上，它的主链具有[-(芳环-肽单元)n-]模式，其构象选择性显著地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、合成、核磁共振和红外光谱相结合的方法，研究人员将研究二聚体到芳酰胺类十二聚体单元在不同溶剂中的构象和能量。这项工作将导致建立一个数据库，最终目标是快速和准确地预测芳香胺的折叠体构象。研究还将产生适当的力场参数，并勾勒出加强折叠器合理设计的一般策略。这项研究的潜在影响是提高了建模的能力，从而设计出具有新应用的新的折叠器。结果和数据将通过同行评议的出版物和在科学会议上的介绍以及通过一个可供公众查阅的数据库提供。根据拟议研究将提供的信息的一般性质，以及其对特定研究的适用性，预计广大科学界，如化学家、生物化学家和材料科学家，以及从事特定研究主题的研究人员，都将从这项研究中受益匪浅。该项目的外展计划包括FDU，一个非授予博士学位的机构，以促进和促进他们在化学方面的研究计划的发展。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.