Conformational Properties of Triazole Foldamers
Title: Conformational Properties of Triazole Foldamers
SNIC Project: SNIC 2019/3-377
Project Type: SNIC Medium Compute
Principal Investigator: Nina Kann <kann@chalmers.se>
Affiliation: Chalmers tekniska högskola
Duration: 2019-07-29 – 2020-08-01
Classification: 10407
Homepage: https://www.chalmers.se/sv/personal/Sidor/nina-kann.aspx
Keywords:

Abstract

Recently, foldamers have emerged as novel artificial oligomers with properties and structural diversity similar to that of natural peptides. Possessing several interesting and important features which their natural representatives lack, they have a great potential for applications in various fields from nanotechnology to pharmaceutics. Among these, foldamers containing 1,4- and 1,5-substitued triazole amino acids are easily prepared and offer increased side chain variation, but their structural capabilities have not yet been widely explored [1]. Earlier we have performed a systematic study exploring the conformational space for the two most important basic units of this set of compounds, the 1,2,4- (4Tzl) and the 1,2,5- (5Tzl) triazole amino acids using quantum chemical exhaustive conformation analysis and solution phase NMR spectroscopy in different solvents [2]. Owing to the computational methods, all conformations of these compounds were scanned and their potential minima were located using several theoretical approaches (e.g. B3LYP/6-311++G(2d,2p), wB97X-D/6-311++G(2d,2p) and MP2/6-311++G(2d,2p) ). Results demonstrate that the 5Tzl derivatives have 11 low energy conformers leading to a great structural diversity with relative energies lying close to each other. In contrast, 4Tzl have much lower amount of energetically stable conformers, which in principle offer only extended conformations. Recently, we have also developed an extension to the CHARMM36m force field for beta-peptides. In a previous application we performed the following: 1. Characterized the conformational properties of all possible chiral building units for both 1,4 and 1,5 triazole amino acids, 2. Built oligomer peptides with folded secondary structures and characterize their properties in view of increasingly complex side chain patterns. We used QM calculations employing B3LYP, wB97XD functionals and middle sized basis sets, to optimize cpu resources [3]. The results were in part used for a review appearing in Chemical Reviews (IF: 48.9) [4]. 3. In the last year we have performed several MD simulations on these compounds, allowing investigation of triazoles and other non-nautral insertions in non-natural oligomers. The continuation of this project aims to address now the conformational properties of these compounds in water, or in a lipid bilayer environments. After the initial tests, it became obvious that we need to perform the following types of calculations: A: Triazole parametrization, using QM calculations and Gaussian B: Investigation of oligomers by MD simulations in water as well as in a lipid bilayer using Gromacs and NAMD. C: The comparison of the folding of triazolamers and beta-peptidic foldamers [1] Johansson, Hermansson, Kann, Nordén, Beke-Somfai, EJOC 2014, 13, 2703 [2] Kann, Johansson, Beke-Somfai, OBC, 2015, 13, 2776 [3] Manuscript submitted [4] Johansson, Beke-Somfai, Said Stalsmeden, Kann,Chemical Reviews, 2016, 116, 14726-14768 [5] Wacha, Beke-Somfai, Nagy, ChemPlusChem, 2019, 84, 927-941