- Protein structure and dynamics
- Intrinsically disordered proteins
- Protein interactions and associated conformational changes in signalling networks relevant to the ubiquitin-proteasome system, autophagy and neurodegeneration
- Structure, dynamics and SNP
induced conformational changes of proteins implicated
in neurodegeneration
My passion has revolved around understanding proteins; their structure, functions and dynamic behaviors. This journey has traversed many stops, from method development to increase accuracy in structural determinations to investigation of changes in that structure using molecular dynamics simulations. The proteins I find most fascinating are those involved in quality control signalling pathways and those implicated in neurodegenerative disease and the relationships between these two groups. My PhD thesis focused on just two proteins in the Ubiquitin-Proteasome pathway, p62-UBA and NBR1-PB1, both believed to be crucial in shuttling misfolded proteins to the proteasome and in autophagy. In my current role this focus has widened to consider 807 proteins of different topologies: the Dynameomics Initiative. This opportunity has allowed me to perform more in-depth surveys of structured and unstructured protein dynamics to gain further understanding of protein behavior across protein fold space. And, as more evidence of the functional roles of intrinsically disordered proteins (IDPs) and regions (IDRs) within signalling networks has accrued, my work has begun to incorporate studies of these fascinating moieties and consideration of the possibility to categorize them into dynamic domain families and in the role of failures in such systems in the onset of human disease.
PhD Chemistry
University of Nottingham Computational Chemistry Group Structural Biology & Biophysics Group
MPhil Chemistry
University of Manchester
NMR Research Group
MChem (Hons) Chemistry University of Leicester
CV (PDF): Updated Jan 2013
I have an experimental background, in industry as well as in academia. Currently, I use molecular dynamic simulations to gain further understanding of protein structure and dynamics at the atomic level. My experiences as both an experimentalist and as a modeller has made me very passionate about the complementary nature of both approaches.
As a senior postdoctoral research fellow withinin the Daggett lab my main focus is the Dynameomics initiative: a dataset of MD simulations of 807 protein domains that represent 97% of all known protein folds. I am currently characterizing the conformational entropies across our Dynameomics database and determining relationships with spectroscopic observables. Due to my interest in IDPs, I have initiated work within the group to examine the presence of disorder across our dataset and have identified a number of targets with known and predicted IDRs. This interesting find is now being examined in greater detail to understand and compare the dynamics and conformational preferences with those of ordered proteins.
- Conformational entropy of structured and unstructured proteins
- Dynamics of intrinsically disordered regions across protein fold space
Poster presented at 2012 GRC on Intrinsically Disordered Proteins
- Clare-Louise Towse, Jiri Vymetal, Jiri Vondrasek and Valerie Daggett, (manuscript in progress)
- Clare-Louise Towse
and Valerie Daggett, "Simulating Protein Folding
Pathways", Reviews in Computational Chemistry
(accepted)
- Clare-Louise Towse and
Valerie Daggett, "When a Domain is not a Domain,
and why it is important to properly
filter proteins in databases", BioEssays,
34, 1060-1069 (2012) [DOI:
10.1002/bies.201200116]
- Clare-Louise Towse
and Valerie Daggett, "Molecular Dynamics
Simulations", In Gordon C. K. Roberts (Ed.),
Encyclopedia of Biophysics, Volume 1, Springer, New
York, Oct 2012 [ISBN
978-3-642-16711-9]
- Ping Chen, Clare-Louise Evans (Clare-Louise Towse), Jonathan D. Hirst and Mark S. Searle, "Structural Insights into the Two Sequential Folding Transition States of the PB1 domain of NBR1 from Φ Value Analysis and Biased Molecular Dynamics Simulations", Biochemistry, (2010) [DOI: 10.1021/bi1016793]
- Clare-Louise Evans, Jed E. Long, Thomas R. A. Gallagher, Jonathan D. Hirst, Mark S. Searle, "Conformation and dynamics of the three-helix bundle UBA domain of p62 from experiment and simulation", Proteins: Structure, Function and Bioinformatics, 71, 227-40 (2008) [DOI: 10.1002/prot.21692]
- Clare-Louise Evans, Gareth A. Morris, and Adrian L. Davis, "A New Method for Variable Temperature Gradient Shimming", Journal of Magnetic Resonance, 154, 325-328 (2002) [DOI: 10.1006/jmre.2001.2497]
"When a Domain is not a Domain"
BioEssays Cover
Dec 2012 Volume 34