Biological

Research in my group can be divided into two areas, although these share a common theme of engineering metal protein interactions in novel ways.

One goal is to engineer novel proteins and polypeptide based assemblies that can be used in molecular electronic devices and nanotechnology in general. This involves understanding, at a fundamental level, how metal cofactors, particularly heme, is delivered to proteins in vivo and, in the case of c-type cytochromes, how heme is covalently attached to protein. It also involves understanding how functional protein units can be assembled into larger nanoscale assemblies that gain function through the proximity of the constituent monomers.

The other goal is to explore the interaction of 4d and 5d tranistion metals with proteins, particularly as a possible route to finding novel medicinal compounds. Specifically, Ruthenium organometallic complexes have shown some potential as anti cancer compounds, but little is understood about how the chemistry of Ruthenium interacts with biomolecules.

Research Interests

Self Assembly of Proteins into functional materials Heme protein assembly and heme chaperones Electrochemistry of Proteins Heavy metal complexes and ther interaction with Proteins

Folates are potential ligands for ruthenium compounds in vivo. TG Scrase, SM Page, PD Barker, SR Boss – Dalton transactions (Cambridge, England : 2003) (2014) 43, 8158 (DOI: 10.1039/c4dt00081a) Local Frustration Determines Molecular and Macroscopic Helix Structures CJ Forman, SN Fejer, D Chakrabarti, PD Barker, DJ Wales – J Phys Chem B (2013) 117, 7918 (DOI: 10.1021/jp4040503) Probing the location of displayed cytochrome b562 on amyloid by scanning tunnelling microscopy. CJ Forman, N Wang, ZY Yang, CG Mowat, S Jarvis, C Durkan, PD Barker – Nanotechnology (2013) 24, 175102 (DOI: 10.1088/0957-4484/24/17/175102) The morphology of decorated amyloid fibers is controlled by the conformation and position of the displayed protein CJ Forman, AA Nickson, SJ Anthony-Cahill, AJ Baldwin, G Kaggwa, U Feber, K Sheikh, SP Jarvis, PD Barker – ACS Nano (2012) 6, 1332 (DOI: 10.1021/nn204140a) Continued surprises in the cytochrome c biogenesis story EB Sawyer, PD Barker – Protein & Cell (2012) 3, 405 (DOI: 10.1007/s13238-012-2912-x) Structural basis for efficient chromophore communication and energy transfer in a constructed didomain protein scaffold JA Arpino, H Czapinska, A Piasecka, WR Edwards, P Barker, MJ Gajda, M Bochtler, DD Jones – Journal of the American Chemical Society (2012) 134, 13632 (DOI: 10.1021/ja301987h) Metastability of native proteins and the phenomenon of amyloid formation. AJ Baldwin, TP Knowles, GG Tartaglia, AW Fitzpatrick, GL Devlin, SL Shammas, CA Waudby, MF Mossuto, S Meehan, SL Gras, J Christodoulou, SJ Anthony-Cahill, PD Barker, M Vendruscolo, CM Dobson – Journal of the American Chemical Society (2011) 133, 14160 (DOI: 10.1021/ja2017703) Metal and redox selectivity of protoporphyrin binding to the heme chaperone CcmE. EM Harvat, O Daltrop, F Sobott, M Moreau, PD Barker, JM Stevens, SJ Ferguson – Metallomics : integrated biometal science (2011) 3, 363 (DOI: 10.1039/c0mt00085j) Aberrant attachment of heme to cytochrome by the Ccm system results in a cysteine persulfide linkage. EB Sawyer, E Stephens, SJ Ferguson, JW Allen, PD Barker – Journal of the American Chemical Society (2010) 132, 4974 (DOI: 10.1021/ja908241v) Tuning heavy metal compounds for anti-tumor activity: is diversity the key to ruthenium’s success? SM Page, SR Boss, PD Barker – Future Med Chem (2009) 1, 541 (DOI: 10.4155/FMC.09.25) Variant c-type cytochromes as probes of the substrate specificity of the E. coli cytochrome c maturation (Ccm) apparatus. JW Allen, EB Sawyer, ML Ginger, PD Barker, SJ Ferguson – Biochem J (2009) 419, 177 (DOI: 10.1042/bj20081999) Interfacial redox processes of cytochrome b562. P Zuo, T Albrecht, PD Barker, DH Murgida, P Hildebrandt – Physical chemistry chemical physics : PCCP (2009) 11, 7430 (DOI: 10.1039/b904926f) Measurement of amyloid fibril length distributions by inclusion of rotational motion in solution NMR diffusion measurements AJ Baldwin, SJ Anthony-Cahill, TP Knowles, G Lippens, J Christodoulou, PD Barker, CM Dobson – Angew Chem Int Ed Engl (2008) 47, 3385 (DOI: 10.1002/anie.200703915) Contribution of rotational diffusion to pulsed field gradient diffusion measurements. AJ Baldwin, J Christodoulou, PD Barker, CM Dobson, G Lippens – The Journal of chemical physics (2007) 127, 114505 (DOI: 10.1063/1.2759211) An induced-fit conformational change underlies the binding mechanism of the heme-transport Proteobacteria-protein HemS M Paoli, S Schneider, K Sharp, P Barker – FASEB JOURNAL (2007) 21, A242 An Induced Fit Conformational Change Underlies the Binding Mechanism of the Heme Transport Proteobacteria-Protein HemS S Schneider, KH Sharp, PD Barker, M Paoli – J Biol Chem (2006) 281, 32606 (DOI: 10.1074/jbc.m607516200) Macroscopic 2D networks self-assembled from nanometer-sized protein/DNA complexes. M Manzanera, DJ Frankel, H Li, D Zhou, A Bruckbauer, P Kreutzmann, JM Blackburn, C Abell, T Rayment, D Klenerman, PD Barker – Nano Lett (2006) 6, 365 (DOI: 10.1021/nl051599+) Cytochrome display on amyloid fibrils. AJ Baldwin, R Bader, J Christodoulou, CE MacPhee, CM Dobson, PD Barker – Journal of the American Chemical Society (2006) 128, 2162 (DOI: 10.1021/ja0565673) Controlling self-assembly by linking protein folding, DNA binding, and the redox chemistry of heme. DD Jones, PD Barker – Angew Chem Int Ed Engl (2005) 44, 6337 (DOI: 10.1002/anie.200463035) Effects of heme on the structure of the denatured state and folding kinetics of cytochrome b562. P Garcia, M Bruix, M Rico, S Ciofi-Baffoni, L Banci, MC Ramachandra Shastry, H Roder, T de Lumley Woodyear, CM Johnson, AR Fersht, PD Barker – Journal of molecular biology (2005) 346, 331 (DOI: 10.1016/j.jmb.2004.11.044)