Flexibility Assessments of Peptide Loops
Peptide loops on the surface of proteins are often very flexible, in that they are known to exist in more than one conformation. Although the word "flexible" has a clear connotation in a qualitative sense, there is no unique index that is a quantifiable measure of molecular flexibility. Such indices are needed in order to compare the relative flexibilities of peptide loops of various lengths and compositions. This project will consist of two components. First, molecular simulations will be used to explore allowed conformations of model peptide loops. Second, both established and novel quantitative measures of flexibility will be examined for their relevancy and ability to describe peptide loop flexibility based on the results of the simulations.
A student undertaking this project will finish with the following knowledge and skill set:
Serum Amyloid A - Conformations and Three-Dimensional Potential Fields
--in collaboration with R. Kisilevsky, Queen's University
Acute phase serum amyloid protein (SAA) is implicated in amyloidoses (undesirable aggregation of proteinaceous filaments) associated with inflammatory response mechanisms. It is known that SAA interacts with constituents of the basement membrane called glycosaminoglycans. Measurements of binding affinity of the glycosaminoglycans heparin and heparan sulphate to various synthetic fragments of SAA have suggested that certain amino acids in the protein are implicated. This project will consist of molecular modelling projects that will address the question as to whether secondary structure predictions of the conformations of SAA are consistent with the requisite distances between the amino acids of SAA implicated in glycosaminoglycan binding. Since the interactions between the glycosaminoglycans and the protein are predicted to be primarily electrostatic in nature, a three-dimensional electrostatic potential map around SAA will be constructed and examined for its ability to elucidate the experimental binding data.
A student undertaking this project will finish with the following knowledge and skill set:
Conformations of Porphyrin Cu2+ - Free Base Heterodimers
--in collaboration with A. van der Est
Photosynthesis takes place in a membrane bound enzyme called a reaction centre via a coupled energy transfer, electron transfer reaction. Covalently linked porphyrin Cu2+ - free base heterodimers are biomimetic complexes of photosynthetic reaction centres. The energy transfer between the triplet state of the free base and the doublet state of the Cu2+ is both distance and orientation dependent. Therefore an understanding of the conformational preferences of the porphyrin heterodimers would be of great utility in relating energy transfer spectra to structure. This project involves a conformational search for low energy conformations of a model porphyrin Cu2+ - free base dimer using a molecular mechanics forcefield. Extensions to quantum mechanical-molecular mechanics (QM/MM) calculations will be considered.
A student undertaking this project will finish with the following knowledge and skill set: