A theoretical study of pentacyclo‐undecane cage peptides of the type [Ac‐X‐Y‐NHMe]

Abstract

The conformational preferences of peptides of the type, Ac-X-Y-NHMe, where X and Y = Ala, cage and Pro, were studied by means of computational techniques within the framework of a molecular mechanics approach. For each of the eight peptide analogues, extensive conformational searches were carried out using molecular dynamics (MD) and simulated annealing (SA) protocols in an iterative fashion. Both results are in good agreement and complement each other. The conformational search indicates that the cage residue restricts the conformational freedom of the dipeptide considerably in comparison with the other model residues used. This study revealed that proline exhibits a greater tendency in promoting reverse-turn characteristics in comparison to the cage peptides, which show promising beta-turn characteristics. It was also found that 300-500 K is not sufficient to overcome rotational barriers for cage peptides. In all cases, the low-energy conformers have a tendency to form bent structures.

Integrated Approach to Structure-Based Enzymatic Drug Design: Molecular Modeling, Spectroscopy, and Experimental Bioactivity

“…Statistical methods are required to ensure that the chances of finding new unique conformations are rather small (see Figure 6). 171 Electronic structure or quantum mechanical (QM) methods based on quantum chemical theory are the most accurate but most expensive calculations in terms of computational resources and time. Such methods include ab initio 176,177 including density functional theory (DFT) 90 Semiempirical methods use QM calculations only for the valence electrons in the system and make drastic approximations for the other electrons as well as the behavior of the atom nuclei.…”

Recent progress on the stereoselective synthesis of cyclic quaternary α-amino acids

“…The structural tendencies of other cyclopropane derivatives such as c 3 Val51,52 or other 2-phenyl-1-aminocycloalkanecarboxylic acids such as c 5 Phe53 and c 6 Phe54–56 have also been reported. Additionally, the theoretical study of 8-aminopentacycloundecane-8-carboxylic acid has been reported 57. Very recently, the helical screw sense exclusively governed by chiral centres in the side chain of some cyclic amino acids has been reported 58–60…”

Charge‐Site‐Dependent Dissociation of Hydrogen‐Rich Radical Peptide Cations upon Vacuum UV Photoexcitation

“…By performing annealing (i.e., slow cooling) from a high temperature, the peptide is able to surmount energetic barriers towards lower energy conformations. This method has been used in a number of gas phase peptide studies 44–47. Ten copies of each of these peptides were annealed from a starting temperature of 1000 K and slowly cooled towards 0 K. The temperature was maintained by using the stochastic thermostat developed by Bussi et al 48.…”