My lab focuses on structural studies of membrane proteins and polypeptides, especially those involved in ion transport and signal transduction. Of particular interest are: voltage-gated sodium channels, calcium channels, antiamoebin , and trichtoxin (polypeptide antibiotics that act as ion channels - see the peptaibol database website), bacteriorhodopsin, endothelin (the most potent vasoconstrictor yet discovered) plus its G-protein coupled receptor ETA, its precursor BigET and its cleavage enzyme ECE. We have developed a new chimeric approach for expression of membrane proteins. We use the techniques of X-ray crystallography, circular dichroism and NMR spectroscopy, cloning and expression, bioinformatics, and molecular modelling, as well as functional studies to examine structure/function relationships.
Methodologically we are developing techniques for synchrotron radiation circular dichroism (SRCD)spectroscopy of proteins, especially for the use of SRCD in Structural and Functional Genomics , and for circular dichroism of membranes, including overcoming solvent shifts, differential scattering, and absorption flattening effects. We have created the DICHROWEB website for secondary structural calculations and a membrane protein CD database. We have also developed a CD data processing and archive package "cdtool" , which is free for academic labs.
In a collaborative project with R.W. Janes of Queen Mary, University of London, we are developing and creating the Protein Circular Dichroism Data Bank (PCDDB), a deposition and archiving data bank and associated validation software for circular dichroism spectra.

Selected Publications:

• Chen, Y., Tucker, A., and Wallace, B.A. (1996) Solution Structure of a Parallel Left-handed Double Helical Gramicidin-A Determined by 2D 1H NMR. J. Mol. Biology 264:757-769.

 
• Doyle, D. and Wallace, B.A. (1997) The Crystal Structure of a Gramicidin/ Potassium Thiocyanate Complex. J. Mol. Biology 266:963-977.

 
• Wallace, B.A. and Corder, R. (1997) Circular Dichroism Studies of Human Big-Endothelin (BigET). J. Peptide Research 49:331-335.

 
• Chen, Y. and Wallace, B.A. (1997) Solvent Effects on the Conformation and Far UV CD Spectra of Gramicidin. Biopolymers 42:771-781.

 
• Riley, M.L., Wallace, B.A., Flitsch, S.L., and Booth, P.J. (1997) Slow alpha helix formation during folding of a membrane protein. Biochemistry 36:192-196.

 
• Chen, Y. and Wallace, B.A. (1997) Secondary Solvent Effects on the Circular Dichroism Spectra of Polypeptides: Influence of Polarisation Effects on the Far Ultraviolet Spectra of Alamethicin. Biophysical Chemistry 65:65-74.

 
• Doyle, D.A. and Wallace, B.A. (1998) Directing the Equilibrium Mixture of Gramicidin Double Helices Towards a Single Conformation with Multivalent Cationic Salts. Biophysical Journal 75:635-640.

 
• Wallace, B.A. (1998) Recent Advances in the High Resolution Structures of Bacterial Channels: Gramicidin A. J. Structural Biology 121:123-141.

 
• Snook, C., Oliva, G., Pattabhi, V., Wood, S., Blundell, T., and Wallace, B.A. (1998) The Structure of Antiamoebin, a Proline-Rich Membrane-Active Polypeptide. Structure 6:783-792.

 
• Duclohier, H., Snook, C.F. and Wallace, B.A. (1998) Antiamoebin Can Function as a Carrier or as a Pore-Forming Peptaibol. BBA (Biomembranes) 1415:255-260.

 
• Rodi, D.J., Janes, R.W., Sanganee, H.J., Holton, R.A., Wallace, B.A., and Makowski, L. (1999) Screening of a Library of Phage-displayed Peptides Identifies Human Bcl-2 as a Taxol-binding Protein. J. Mol. Biology 285:197-203./

 
• Cronin, N. and Wallace, B.A. (1999) Do the Structures of Big ET-1 and Big ET-3 Adopt a Similar Overall Fold? Consequences for Endothelin Converting Enzyme Specificity. Biochemistry 38:1721-1726.

 
• Hanlon, M.R., Berrow, N.S., Dolphin, A.C., and Wallace, B.A. (1999) Modelling of the Voltage-Dependent Ca++ Channel Beta subunit as a Basis for Understanding its Functional Properties. FEBS Letts. 445:366-370.

 
• Wallace, B.A. (1999) Circular Dichroism Spectrsocopy and X-ray Crystallography: A Dynamic Duo. CCP4 Newletter 37:29-30.

 
• Wallace, B.A. and Janes, R.W. (1999) Tryptophans in Membrane Proteins: X-ray Crystallographic Analyses. Adv. Exp. Med. Biol. 467:789-799.

 
• Snook, C.P. and Wallace, B.A. (1999) The Molecular Replacement Solution of an Intermediate-Sized Polypeptide, Antiamoebin I. Acta Cryst. D55:1539-1545.

 
• Wallace, B.A. (2000) Common Structural Features in Gramicidin and Other Ion Channels. Bioessays 22:227-234.

 
• Wallace, B.A. (2000) Conformational Changes by Synchrotron Radiation Circular Dichroism Spectroscopy. Nature Structural Biology 7:708-709.

 
• Fischer, W.B., Pitkeathly, M., Wallace, B.A., Forrest, L.R., Smith, G.R., and Sansom, M.S.P. Transmembrane Peptide NB of Influenza B: A Simulation, Structure, and Conductance Study. Biochemistry 39:12708-12716.

 
• Hanlon, M.R., Begum, R.R. Newbold, R.J., Whitford, D., and Wallace, B.A. In vitro membrane-inserted conformation of the cytochrome b5 tail. Biochemical Journal 352:117-124.

 
• Cid, G.M., Nugent, P.G., Davenport, A.P., Kuc, R.E., and Wallace, B.A. (2000) Expression and Characterisation of the Human Endothelin A Receptor in Pichia pastoris: Influence of N-terminal Epitope Tags. J. Cardio. Pharm. 36:S55-S56.

 
• Wallace, B.A. (2000) Synchrotron Radiation Circular-Dichroism Spectroscopy as a Tool for Investigating Protein Structures. J. Synchrotron Radiation 7:289-295.

 
• Clarke, DT., Bowler, M.A., Fell, B.D., Flaherty, J.V., Grant, A.F., Jones, G.R., Martin-Fernandez, M.L., Shaw, D.A., Todd, B., Wallace, B.A., and Towns-Andrews, E. (2000) A high aperature beamline for vacuum ultraviolet circular dichroism on the SRS. Synchrotron Radiation News 13:21-27.

 
• Orry, A.J.W. and Wallace, B.A. (2000) Modeling and Docking the Endothelin G-Protein Coupled Receptor. Biophysical J. 79:3083-3094.

 
• Orry, A.J.W., Janes, R.W., Sarra, R., Hanlon. M.R., Wallace, B.A. (2001) Synchrotron Radiation Circular Dichroism Spectroscopy: Vacuum Ultraviolet Irradiation Does Not Damage Protein Integrity. J. Synchrotron Radiation 8:1027-1029.

 
• Chugh, J.K. and Wallace, B.A. (2001) Peptaibols: Models for Ion Channels. Biochemical Society Transactions 29:567-571.

 
• Wallace B.A. and Janes, R.W. (2001) Synchrotron Radiation Circular Dichroism Spectroscopy of Proteins: Secondary Structure, Fold Recognition and Structural Genomics. Curr. Opin. Chemical Biology 5:567-571.

 
• Hanlon, M. and Wallace, B.A. (2002) Structure and Function of Voltage Dependent Ion Channel Regulatory Beta Subunits. Biochemistry 41:2886-2894.

 
• Lobley, A., Whitmore, L., and Wallace, B.A. (2002) DICHROWEB: An Interactive Website for the Analysis of Protein Secondary Structure from Circular Dichroism Spectra. Bioinformatics 18:211-212.

 
• Wallace, B.A. (2002) First International Workshop on SRCD Spectroscopy. Synchrotron Radiation News 15:20-22.

 
• Lawton, D.G., Longstaff, C., Wallace, B.A., Hill, J., Leary, S.E.C., Titball, R.W., and Brown, K.A. (2002) Interactions of the Type III Secretion Pathway Proteins LcrV and LcrG from Yersinia pestis are Mediated by Coiled-Coil Domains. J. Biol. Chem. 277: 38714-38722.

 
• Porcelli, I., de Leeuw, E., Wallis, R., van den Brink-van der Lann, E., de Kruijff, B., Wallace, B.A., Palmer, T., and Berks, B.C. (2002) Characterization and Membrane Assembly of the TatA Component of the Escherichia coli Twin-Arginine Protein Transport System. Biochemistry 41:13690-13697.

 
• Chugh, J.K., Bruckner, H., and Wallace, B.A. (2002) Model for a Helical Bundle Channel Based on the High-Resolution Crystal Structure of Trichotoxin_A50E. Biochemistry 41:12934-12941.

journal cover
 
• Lees, J.G., and Wallace, B.A. (2002) Synchrotron Radiation Circular Dichroism and Conventional Circular Dichroism Spectroscopy: A Comparison. Spectroscopy 16:121-125.

 
• O'Boyle, F., and Wallace, B.A. (2003) The Temperature Dependence of Gramicidin Conformational States in Octanol. Prot. Peptide Letters 10:9-17.

 
• Galbraith, T.P., Harris, R., Driscoll, P.C., Wallace, B.A. (2003) Solution NMR Studies of Antiamoebin, a Membrane Channel-Forming Polypeptide. Biophysical Journal 84:185-194.

 
• Cronin, N.B., O'Reilly, A.O., Duclohier, H., Wallace, B.A. (2003) Binding of the Anticonvulsant Drug Lamotrigine and the Neurotoxin Batrachotoxin to Valtage-gated Sodium Channels Induces Conformational Changes Associated with Block and Steady-state Activation. J. Biol. Chem. 278:10675-10682.

 
• Wallace, B.A., Lees, J.G., Orry, A.J.W., Lobley, A., and Janes, R.W. (2003) Analyses of Circular Dichroism Spectra of Membrane Proteins. Protein Science 12:875-884.

 
• Wallace, B.A. and Janes, R.W. (2003) Circular Dichroism and Synchrotron Radiation Circular Dichroism Spectroscopy: Tools for Drug Discovery. Biochemical Transactions 31:631-633.

 
• O'Reilly, A.O. and Wallace, B.A. The Peptaibol Antiamoebin as a Model Ion Channel: Similarities to Bacterial Potassium Channels. J. Pept. Sci. 9:769-775.

 
• Whitmore, L., Chugh, J.K., Snook, C.F. and Wallace, B.A. The Peptaibol Database - A Sequence and Structure Resource. J. Pept. Sci. 9:663-665.

 
• Miles, A.J., Wien, F., Lees, J.G., Rodger, A., Janes, R.W., and Wallace, B.A. (2003) Calibration and Standardisation of Synchrotron Radiation Circular Dichroism (SRCD) Amplitudes and Conventional Circular Dichroism (CD) Spectrophotometers. Spectroscopy 17:653-661.

 
• Wallace, B.A., Wien, F., Miles, A.J., Lees, J.G., Hoffman, S.V., Evans, P., Wistow, G.J., and Slingsby, C. (2004) Biomedical applications of synchrotron radiation circular dichroism spectroscopy: Identification of mutant proteins associated with disease and development of a reference database for fold motifs. Faraday Discussions 17:653-661.

 
• Whitmore, L. and Wallace, B.A. (2004) DICHROWEB, An Online Server For Protein Secondary Structure Analyses from Circular Dichroism Spectroscopic Data. Nucleic Acids Research 32:W668-673.

 
• Duclohier, H., Alder, G.M., Bashford, C.L., Brückner, H., Chugh, J.K., and Wallace, B.A. 2004. Conductance Studies on Trichotoxin_A50E and Implications for Channel Structure. Biophysical J. 87:1705-1710.

 
• Whitmore, L., and Wallace, B.A. (2004) The Peptaibol Database: A database for sequences and structures of naturally occurring peptaibols. Nucleic Acids Research 32: D593-D594.

 
• Evans, P., Wyatt, K., Wistow, G.J., Bateman, O.A., Wallace, B.A., and Slingsby, C. (2004) The P23T Cataract Mutation Causes Loss of Solubility of Folded gD-Crystallin. J. Mol. Biology 343:435-444.

 
• Lees, J.G., Smith, B.R., Wien, F., Miles, A.J., and Wallace, B.A.. (2004) CDtool - An Integrated Software Package for Circular Dichroism Spectroscopic Data Processing, Analysis and Archiving. Analytical Biochemistry 332:285-289.

 
• Miles, A.J., Whitmore, L., and Wallace, B.A. (2005) Spectral Magnitude Effects on the Analyses of Secondary Structure from Circular Dichroism Spectroscopic Data. Protein Science 14:368-374.

 
• Miles, A.J., Wien, F., and Wallace, B.A. (2004) Redetermination of the Extinction Coefficient of Camphor-b-Sulfonic Acid, a Calibration Standard for Circular Dichroism Spectroscopy. Analytical Biochemistry 335:338-339.

 
• Miles, A.J., Wien, F., Lees, J.G., and Wallace, B.A. (2005) Calibration and Standardisation of Synchrotron Radiation and Conventional Circular Dichroism Spectrometers. Part 2: Factors Affecting Magnitude and Wavelength. Spectroscopy 19:43-51.

 
• Cronin, N.B., O'Reilly, A., Duclohier, H., and Wallace, B.A. (2005) Effects of Deglycosylation of Sodium Channels on their Structure and Function. Biochemistry 44:441-449.

 
• Miles, A.J., Whitmore, L., and Wallace, B.A. (2005) Spectral Magnitude Effects on the Analyses of Secondary Structure from Circular Dichroism Spectroscopic Data. Protein Science 14:368-374.

 
• Wallace, B.A. (2005) Shining New Light on Protein Structure and Function thru Synchrotron Radiation Circular Dichroism (SRCD) Spectroscopy. Australian Biochemist 36: 47-50.

 
• O'Reilly, A.O., Khambay, B.P.S., Williamson, M.S., Field, L.M., Wallace, B.A. and Davies, T.G.E. (2006) Modelling insecticide binding sites at the voltage-gated sodium channel. Biochemical Journal 396:255-263.

journal cover
 
• Whitmore, L., Janes, R.W., and Wallace, B.A. (2006) Protein Circular Dichroism Data Bank (PCDDB): Data Bank and Website Design.

Chirality 18:426-429.
 
• Wallace, B.A., Whitmore, L., and Janes, R.W. (2006) The Protein Circular Dichroism Data Bank (PCDDB): A Bioinformatics and Spectroscopic Resource. Proteins: Structure, Function and Bioinformatics 62:1-3.

 
• Miles, A.J. and Wallace, B.A. (2006) Synchrotron Radiation Circular Dichroism Spectroscopy of Proteins and Applications in Structural and Functional Genomics. Chem. Soc. Reviews 35:39-51.

 
• Lees, J.G., Miles, A.J., Wien, F., and Wallace, B.A. (2006) A reference database for circular dichroism spectroscopy covering fold and secondary structure space. Bioinformatics 22:1955-1962.

 
• Lees, J.G., Miles, A.J., Janes, R.W., Wallace, B.A. (2006) Optimisation and development of novel methodologies for secondary structure prediction from circular dichroism spectra. BMC Bioinformatics 7:507-517.

 
• Evans, P., Bateman, O.A., Slingsby, C., and Wallace, B.A. (2007) A Reference Dataset for Circular Dichroism Spectroscopy Tailored for the ß?-Crystallin Lens Proteins. Experimental Eye Research 84:1001-1008.

 
• McKibbin, C., Farmer, N.A., Jeans, C., Reeves, P.J., Khorana, H.G., Wallace, B.A., Edwards, P.C., Villa, C., and Booth, P.J. (2007) Opsin Stability and Folding: Modulation by Phospholipid Bicelles. J. Mol. Biol. 374:1319-1332.

 
• Miles, A.J., Hoffman, S.V., Tao, Y., Janes, R.W., and Wallace, B.A. (2007) Synchrotron radiation circular dichroism (SRCD) spectroscopy: New beamlines and new applications in biology, Spectroscopy 21:245-255.

 
• Evans, P., Slingsby, C., and Wallace, B.A. (2008) Association of Partially-Folded Lens ßB2-Crystallins with the a-Crystallin Molecular Chaperone. Biochemical Journal 408:691-699.

 
• Cowieson, N.P., Miles, A.J., Robin, G., Forwood, J.K., Kobe, B., Martin, J.L., and Wallace, B.A. (2008) Evaluating Protein: Protein Complex Formation using Synchrotron Radiation Circular Dichroism Spectroscopy. Proteins: Structure Function Bioinformatics 70:1142-1146.

 
• Bulheller, B., Miles, A.J., Wallace, B.A., and Hirst, J. (2008) Charge-transfer transitions in the vacuum ultraviolet of protein circular dichroism spectra. J. Phys. Chem. B 112:1866-1874.

 
• Whitmore, L., and Wallace, B.A. (2008) Protein Secondary Structure Analyses from Circular Dichroism Spectroscopy: Methods and Reference Databases. Biopolymers 89:392-400.

 
• Miles, A.J., Drechsler, A., Kristan, K., Anderluh, G., Norton, R.S., Wallace, B.A. and Separovic, F. (2008) The effects of lipids on the structure of the eukaryotic cytolysin equinatoxin II: a synchrotron radiation circular dichroism spectroscopic study. BBA (Biomembranes) 1778: 2091-2096.

 
• Lampert, A., O’Reilly, A.O., Dib-Hajj, S.D., Tyrrell, L., Wallace, B.A., and Waxman, S.G. (2008) A pore-blocking hydrophobic motif at the cytoplasmic aperture of the closed-state Nav1.7 channel is disrupted by the erythromelalgia-associated F1449V mutation. J. Biol. Chem. 283:24118-24127.

 
• Nurani, G., Radford, M., Charalambous, K., O’Reilly, A.O., Cronin, N., Haque, S., and Wallace, B.A. (2008) Tetrameric Bacterial Sodium Channels: Characterisation of Structure, Stability, and Drug Binding. Biochemistry 47:8114-8121.

 
• O’Reilly, A.O., Charalambous, K., Nurani, G., Powl, A.M. and Wallace, B.A. (2008) G219S Mutagenesis as a Means of Stabilising Conformational Flexibility in the Bacterial Sodium Channel NaChBac. Molecular Membrane Biology 25: 670-676.

Our work is supported by grants from the BBSRC, the Wellcome Trust, the British Heart Foundation, and CNRS/The Royal Society.
In collaboration with Dr. Alison Rodger of Warwick University, we have run an EPSRC-sponsored summer school in CD Spectroscopy for the past 5 years and will do so again in 2008. Each summer in conjunction with Dr. J. Sutherland we run a training course, BioCD, at Brookhaven National Laboratory.
 

Current Group Members