Professor Lorna Smith
Professor of Chemistry
Our research is concentrated around characterising native and non-native protein folds. The work has significance for our understanding of disease states relating to protein misfolding (such as Alzheimer's and Parkinson's disease), drug design and food allergies (especially to the pan-allegen lipid transfer proteins) as well as providing fundamental insights into the determinants of protein structure, folding and dynamics. Our research combines experimental and theoretical approaches and particularly uses molecular dynamics simulations in combination with data from high-resolution NMR techniques. Models from the MD simulations provide a framework for interpreting experimental data while the experimental results help prompt new theoretical developments.
Studies of native state protein dynamics
The importance of dynamics in the functional roles of native folded proteins is being increasingly recognised. Current projects in this area include:
- Studies of the effects of substrate binding on the dynamics of the flexible lip regions of the enzyme lambda lysozyme.
- Using MD simulations to identify how subtle sequence changes between lipid transfer proteins from different species give rise to significantly different ligand binding modes and preferences.
- Characterisation of the loop dynamics and hinge bending in four-helix bundle proteins including growth hormone, prolactin and interleukin-4,
- Development of novel approaches for using NMR parameters as experimental restraints in MD simulations (especially spin-spin coupling constants, order parameters and residual dipolar coupling constants).
Studies of non-native protein conformations
The study of non-native partly folded, misfolded and denatured protein conformations is particularly challenging, as these states are often highly flexible systems in which multiple conformers are being adopted. Here our current projects include:
- Development of models for non-native states of alpha-lactalbumin seen under low pH conditions using NMR and EPR data.
- Characterisation of misfolded forms of cyclophilin D, a peptidyl-prolyl isomerase, with non-native disulphide bridges.
- Modelling non-native states of proteins seen in the presence of organic solvents such as trifluoroethanol.
- Studies of polypeptides containing modified amino acid residues.
- A focus on understanding of the effects of post-translational modifications, such as glycosylation or phosphorylation, on native and non-native protein folds.
Lorna J Smith is a Professor of Chemistry and the Peacock Tutorial Fellow at St. Hilda's College. Her research uses a combination of experimental and theoretical approaches to characterise native and non-native protein folds. Lorna has a long-term collaboration with Wilfred van Gunsteren and co-workers at the ETH in Zurich where she was a visiting professor in 2010. From 1994-2001, Lorna was a Royal Society University Research Fellow and prior to that a Junior Research Fellow at St. Cross College Oxford. Both these fellowships were held in the Oxford Centre for Molecular Sciences. Lorna studied for both her BA and D.Phil. in Chemistry at the University of Oxford (Lady Margaret Hall) and did her D.Phil. in the lab of Chris Dobson using 3D NMR techniques, which were at that time very new, to determine the structures of the proteins human interleukin-4 and hen lysozyme in solution.