The role of hydration water in the equilibrium polymerisation of tubulin with and without nucleotides (ATP and GTP) and anticancer agents

DOI

We propose to investigate the role of water and of hydrogen bonding at the water-protein interface in the polymerisation of tubulin ab-hetero-dimers into microtubules, using Quasi-Elastic and Elastic Neutron Scattering with the high-resolution spectrometer IRIS.The experimental results will allow us to quantify the vibrational Mean Square Displacement of protein atoms, and the diffusion coefficient of solvent (water) molecules. These data, in turn, will provide a direct view of the entropy changes across polymerisation, which, in the case of tubulin, is known to be entropy driven. A series of additional measurements has been planned to identify the role of nucleotides (GTP and GDP) bound to tubulin, as well as the effect of taxol, whose remarkable anti-cancer activity is due to its ability to stabilise microtubules with respect to the oligomeric phase.

Identifier
DOI https://doi.org/10.5286/ISIS.E.42583284
Metadata Access https://icatisis.esc.rl.ac.uk/oaipmh/request?verb=GetRecord&metadataPrefix=oai_datacite&identifier=oai:icatisis.esc.rl.ac.uk:inv/42583284
Provenance
Creator Professor Don Kearley; Dr Antonio Benedetto; Dr Gonzalez; Professor Pietro Ballone; Dr Sanghamitra Mukhopadhyay; Professor Felix Fernandez-Alonso; Dr Miguel Angel Gonzalez
Publisher ISIS Neutron and Muon Source
Publication Year 2017
Rights CC-BY Attribution 4.0 International; https://creativecommons.org/licenses/by/4.0/
OpenAccess true
Contact isisdata(at)stfc.ac.uk
Representation
Resource Type Dataset
Discipline Biology; Biomaterials; Engineering Sciences; Life Sciences; Materials Science; Materials Science and Engineering; Medicine; Natural Sciences; Physics
Temporal Coverage Begin 2014-03-28T00:00:00Z
Temporal Coverage End 2014-04-03T23:00:00Z