Arthur M. Lesk Professor of Biochemistry and Molecular Biology 512A Wartik Laboratory, University Park, PA 16802 Phone: (814) – 865-4743 Fax: (814) 863-1357 Email: aml25@psu.edu A.B., in biochemical sciences, Harvard University Ph.D. in physics and physical chemistry, Princeton University M.A., University of Cambridge Lesk Lab Web Site

Protein Structure, Function and Evolution

Major research interests:

Protein evolution: Discovery of the relationship between changes in amino acid sequence and changes in protein structure, through analysis of the mechanism of evolution in protein families. These investigations have provided a quantitative basis for homology modelling, currently the most successful and widely used method of structure prediction.

Conformations of antigen-binding sites of immunoglobulins and related proteins: Development of the "canonical-structure model" for the conformation of the complementarity- determining regions of antibodies, and its application to prediction of structure and to analysis of antibody germ line genes. This work has supported the "humanization" of antibodies for therapy. These investigations are now being extended to other groups of molecules in the immunoglobulin superfamily, including T-cell receptors and cell-adhesion molecules.

Mechanisms of conformational change: Detailed comparisons of proteins in different structural states. Discovery of the helix-interface shear mechanism as an alternative to hinge bending, and analysis of conformational changes in proteins that show these mechanisms. Application to conformational changes in serine-protease inhibitors (serpins) and their interactions with proteases.

Systematic analysis of protein folding patterns: Development of a mathematical representation of folding patterns and its application to fold classification and recognition.

Molecular graphics: Authorship of the first program to generate schematic diagrams of proteins by computer; development of many algorithms in the field of structural analysis.

Representative Publications:

• Arthur M. Lesk (2007).  Introduction to Genomics. Oxford University Press.
• Vineet Sangar, Daniel J. Blankenberg, Naomi Altman and Arthur M. Lesk (2007). Quantitative sequence-function relationships in proteins based on Gene Ontology. BMC Bioinformatics 8, 294.
• Akhil Kamat and Arthur M. Lesk (2007). Contact patterns between helices and strands of sheet define protein folding patterns. Proteins: Structure, Function and Bioinformatics 66, 869-876.
• David Zanuy, Kannan Gunasekaran, Arthur M. Lesk and Ruth Nussinov (2006). Computational study of the fibril organization of polyglutamine repeats reveals a common motif identified in beta-helices. Journal of Molecular Biology 358, 330-345.
• Arun S. Konagurthu, Peter J. Stuckey, James C. Whisstock, and Arthur M. Lesk (2006). MUSTANG: A MUltiple STructural AligNment AlGorithm. Proteins: Structure, Function and Bioinformatics 64, 559-574.
• Timothy Lezon, Jayanth R. Banavar, Arthur M. Lesk and Amos Maritan (2006). What determines the spectrum of protein native state structures? Proteins: Structure, Function and Bioinformatics 63, 273-277.
• Melik C. Demirel & Arthur M. Lesk (2005). Molecular forces in antibody maturation. Physical Review Letters 90, 208106.
• David A. Vuletich, Juliette T. Lecomte & Arthur M. Lesk (2005). Structural divergence and distant relationships in proteins: evolution of the globins. Current Opinion in Structural Biology 15, 290-301.
• Arthur M. Lesk (2005). Complexity in biological structures and systems. In: Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics, Vol. 7, pp. 3298-3321. L.B. Jorde, P.F.R. Little, M.J. Dunn & S. Subramaniam, Eds., Chichester, John Wiley & Sons, Ltd.
• James C. Whisstock and Arthur M. Lesk (2003). Prediction of protein function from protein sequence and structure. Quarterly Review of Biophysics, 36, 307-340.
• Arthur M. Lesk (2002). Introduction to Bioinformatics Oxford: Oxford University Press. See: http://www.oup.co.uk/isbn/0-19-925196-7.
• Arthur M. Lesk (2001). Introduction to Protein Architecture: The Structural Biology of Proteins Oxford: Oxford University Press. See: http://www.oup.co.uk/isbn/0-19-850474-8
• Peter Mastrangelo, Louise Serpell, Timothy Dafforn, Arthur Lesk, Paul Fraser and David Westaway (2002). A cluster of familial Creutzfeldt-Jakob disease mutations recapitulate conserved residues in Doppel: a case of molecular mimicry? FEBS Lett. 532, 21-26.
• Max F. Perutz, John T Finch, John Berriman and Arthur M. Lesk (2002). Amyloid fibers are water-filled nanotubes. Proc. Nat. Acad. Sci. (USA). 99, 5591-5595.
• Arthur M. Lesk, Loredana Lo Conte and Tim J.P. Hubbard (2001). Assessment of novel fold predictions in CASP4. Proteins: Structure, Function and Genetics, 45 (Supplement 5), 98-118.
• James A. Irving, James C. Whisstock and Arthur M. Lesk (2001). Protein structural alignments and functional genomics. Proteins: Structure, Function and Genetics 42, 378-382.
• James A. Irving, Robert N. Pike, Arthur M. Lesk, and James C. Whisstock (2000). Phylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function. Genome Research 10, 1845-1864.
• Arthur M. Lesk and 25 co-authors. (2000). Quality control in databanks for molecular biology. BioEssays 22, 1024-1034.

Search the MEDLINE database at PubMed for articles by A Lesk