My lab focuses on structure/function studies of membrane proteins and polypeptides, especially those involved in ion transport and signal transduction. Of particular interest are voltage-gated sodium channels (we have recently determined the first crystal structure of a sodium channel in its open conformation ) and polypeptide ion channels such as antiamoebin , and trichtoxin (polypeptide antibiotics that act as ion channels). We have developed a new chimeric approach for expression of membrane proteins, and have produced a functional "minimal" sodium channel pore . We use the techniques of X-ray crystallography and circular dichroism spectroscopy, cloning and expression, bioinformatics, and molecular modelling, as well as functional studies to examine structure/function relationships for these ion channels.

Methodologically, we develop techniques and applications for synchrotron radiation circular dichroism (SRCD)spectroscopy of proteins, especially for its use of SRCD in Structural and Functional Genomics, and for circular dichroism of membrane proteins, including ways of mitigating solvent shifts, differential scattering, and absorption flattening effects. We have created the DICHROWEB website for secondary structural calculations , new soluble and membrane protein reference databases for CD analyses, a CD data processing and archive package "CDtool" for use with conventional CD and SRCD beamline data.

In a collaborative project with R.W. Janes of Queen Mary, University of London, we have created the Protein Circular Dichroism Data Bank (PCDDB), a deposition and archiving data bank and associated validation software for circular dichroism spectra and the DichroMatch method for structural analyses.

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.
• Charalambous, K., O'Reilly, A.O., Bullough, P., and Wallace, B.A. (2009) Thermal and chemical unfolding and refolding of a eukaryotic sodium channel. Biochim. Biophys. Acta (Biomembranes) 1788:1278-1286.
• Drechsler, A., Miles, A.J., Norton, R.C., Wallace, B.A. and Separovic, F. (2009) Effect of Lipid on the Conformation of the N-Terminal Region of Equinatoxin II: A Synchrotron Radiation CD Study. European Biophysics Journal 39:121-127.
• Wallace, B.A. (2009) Protein Characterisation by Synchrotron Radiation Circular Dichroism Spectroscopy. Quarterly Reviews of Biophysics 42:317-370.
• Wallace, B.A. and Janes, R.W. (2010) Synchrotron Radiation Circular Dichroism (SRCD) Spectroscopy - An Enhanced Method for Examining Protein Conformations and Protein Interactions. Biochemical Society Transactions 38:861-873.
• Kintzer, A.F., Sterling, H.J., Tang, I.I., Abdul-Gader, A., Miles, A.J., Wallace, B.A., Williams, E.R., and Krantz, B.A. (2010) Role of the protective antigen octamer in the molecular mechanism of anthrax lethal toxin stabilization in plasma. J. Mol. Biol. 399:741-758.
• Powl, A.M., O'Reilly, A.O., Miles, A.M. and Wallace, B.A. (2010) Synchrotron radiation circular dichroism spectroscopy-defined structure of the C-terminal domain of NaChBac and its role in channel assembly. Proc. Natl. Acad. Sci. (USA) 107: 14064-14069.
• Zhai, J., Pattenden, L.K., Miles, A.J., Lee, T-H., Augustin, M.A., Wallace, B.A., Aguilar, M-I., and Wooster, T.J. (2010) Changes in beta-lactoglobulin conformation at the oil/water interface of emulsions studied by synchrotron radiation circular dichroism. Biomacromolecules 11: 2136-2142.
• Klose, D.P., Wallace, B.A. and Janes, R.W. (2010) 2Struc: The Secondary Structure Server. Bioinformatics 26:2624-2625.
• Meersman, F., Atilgan, C., Miles, A.J., Bader, R., Shang, W., Matagne, A., Wallace, B.A., and Koch, M.H.J. (2010) Consistent picture of the reversible thermal unfolding of hen egg-white lysozyme from experiment and molecular dynamics. Biophysical J. 99:2255-2263.
• Whitmore, L., Woollett, B., Miles, A.J., Janes, R.W., and Wallace, B.A. (2010) The Protein Circular Dichroism Data Bank - A Web-based Site for Access to Circular Dichroism Spectroscopic Data. Structure 18:1267-1269.
• Moore, B., Miles, A.J., Guerra-Giraldez, C., Simpson, P., Iwata, M., Wallace, B.A., Matthews, S.J., Smith, D.F., and Brown, K.A. (2011) Structural Basis of Molecular Recognition of the Leishmania Small Hydrophilic Endoplasmic Reticulum-associated Protein (SHERP) at Membrane Surfaces. J. Biol. Chem. 286:9246-9256.
• Wallace, B.A., Gekko, K., Hoffmann, S.V., Lin, Y-H., Sutherland, J.C., Tao, Y., Wien, F., and Janes, R.W. (2011) Synchrotron Radiation Circular Dichroism (SRCD) Spectroscopy - An Emerging Method in Structural Biology for Examining Protein Conformations and Protein Interactions. Nuclear Instrumentation and Methods , in press. doi:10.1016/j.nima.2010.10.135
• Beich-Frandsen, M., Vecerek, B. Konarev, P.V., Sjoblom, B., Kloiber, K., Hammerle, H., Rajkowitsch, L., Miles, A.J., Kontaxis, G., Wallace, B.A., Svergun, D.I., Konrat, R., Blasi, U. and Djinovic-Carugo, K. (2011) S tructural insights into the dynamics and function of the C-terminus of the E. coli RNA chaperone Hfq. Nucleic Acids Research , 39:4900-4915.
• Whitmore, L., Woollett, B., Miles, A.J., Klose, D.P., Janes, R.W., and Wallace, B.A.(2011) PCDDB: The Protein Circular Dichroism Data Bank, A Repository for Circular Dichroism Spectral and Metadata. Nucleic Acids Research 39:D480-D486.
• McCusker, E.C., D'Avanzo, N., Nichols, C.G., and Wallace, B.A. (2011) Simplified Bacterial "Pore" Provides Insight into the Assembly, Stability and Structure of Sodium Channels. J. Biol. Chem. 286:16386-16391.
• McCusker, E.C., Bagneris, C., Naylor, C.E., Cole, A.R., D'Avanzo, N., Nichols, C.G., and Wallace, B.A. (2012) Structure of a Bacterial Voltage-Gated Sodium Channel Pore Reveals Mechanisms of Opening and Closing. Nature Communications , in press.