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Back to basics: fundamentals forces in protein structure, design & interactions

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Despite considerable effort, the fundamental forces that underpin protein folding, form and function are not fully understood. Using a combination of bioinformatics, computational biochemistry, and peptide design, synthesis and characterisation, my group is exploring some of the non-covalent forces at play in protein folding and assembly, and in protein-small molecule interactions. This talk will describe some of our recent work on: electrostatic and n-to-π star interactions in α-helices [1,2]; how hydrophobic and van der Waals’ interactions can be designed to direct the assembly of entirely new α-helical barrel structures [3]; and how natural proteins bind and distinguish between different carbohydrate moieties through electrostatic complementary and CH-π star interactions [4]. Time allowing, I will also describe how we are creating standard peptide components to assemble new supramolecular objects [5].

1. n-to-π* Interactions in proteins GJ Bartlett, A Choudhary, RT Raines, and DN Woolfson Nature Chemical Biology 6, 615-620 (2010)

2. Local and macroscopic electrostatic interactions in single α−helices EG Baker, GJ Bartlett, MP Crump, RB Sessions, N Linden, CFJ Faul, and DN Woolfson Nature Chemical Biology 11, 221-8 (2015)

3. Computational design of water-soluble α−helical barrels. AR Thomson, CW Wood, AJ Burton, GJ Bartlett, RB Sessions, RL Brady, and DN Woolfson Science 346, 485-488 (2014)

4. An electronic component to CH-π interactions in protein-carbohydrate complexes KL Hudson, GL Bartlett, RC Diehl, J Agirre, T Gallagher, LL Kiessling, and DN Woolfson Submitted

5. Self-assembling cages from coiled-coil peptide modules JM Fletcher, RL Harniman, FRH Barnes, AL Boyle, A Collins, J Mantell, TH Sharp, M Antognozzi, PJ Booth, N Linden, MJ Miles, RB Sessions, P Verkade, and DN Woolfson Science 340, 595-599 (2013)

This talk is part of the Theory - Chemistry Research Interest Group series.

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