Conformational Analysis of Cyclic Tetra-Peptides by Global Energy Minimisation Calculations

Morrow, Christopher (1978) Conformational Analysis of Cyclic Tetra-Peptides by Global Energy Minimisation Calculations. PhD thesis, University of Glasgow.

Abstract

An algorithm, based on Molecular Mechanics calculations, was developed to locate the Global Minimum Energy Conformation (GMEC) of cyclic molecules. This was used to find the GMEC of cyclotetraglycyl and also those conformations within 20 kcal/mole of this conformation. The resulting conformation is composed of four trans amino acids and has S4 symmetry. The calculated GMEC corresponds to an observed crystal structure of dihydrochlamydocin and to a proposed conformation of cyclotetraglycyI itself. The ring conformations of all observed cyclic tetra -peptides and -depsipeptides were found to correspond, more or less exactly, to some conformation in the calculated low energy set of cyclotetraglycyl. Only one exception was found and this seems to be an intermediate between two calculated conformations. The algorithm has now been further streamlined into a single computer program and is currently being used to locate the GMEC of cycloalkanes (e. g. cycloundecane) in this department and elsewhere. Calculations were also performed on various derivatives of cyclotetraglycyl. Protonation and N-Methylation were found to profoundly alter the relative energies of the various conformations in the low energy set. It was observed that for these derivatives the cis, trans, cis, trans sequence of amino acids is more stable than the all trans sequence. In addition to peptides the conformations of other 12-membered rings were found to correspond to members of the calculated set of conformations. These included 12-crown-4 ethers and cyclododecanes. In order to facilitate all of these operations a Chemical Graphics System (CGS) was developed. This is an extensive suite of computer programs which utilises a PDP11/40 minicomputer with a VR17 graphics terminal. The CCS allows interactive building and manipulation of molecular models and includes various advanced features. Foremost of these is the dynamic rotation facility which allows the user to observe a structure as it rotates about the X, Y or Z axis. Measurement of distances. angles and torsion angles is easy and the constructed structure can be directly used as input to a Molecular Mechanics calculation.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Computational chemistry, Physical chemistry
• Date of Award: 1978
• Depositing User: Enlighten Team
• Unique ID: glathesis:1978-78797
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 14:53
• Last Modified: 30 Jan 2020 14:53
• URI: https://theses.gla.ac.uk/id/eprint/78797