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Arthur M. Lesk
Arthur M. Lesk, is an accomplished protein science researcher, who is currently a professor of biochemistry and molecular biology at the Pennsylvania State University, University Park.
Additional recommended knowledge
Lesk has made significant contributions to the study of protein evolution. He and Cyrus Chothia, working at the MRC Laboratory of Molecular Biology in Cambridge, United Kingdom, discovered the relationship between changes in amino-acid sequence and changes in protein structure by analyzing the mechanism of evolution in protein families. This discovery has provided the quantitative basis for the most successful and widely used method of structure prediction, know as homology modelling.
Lesk and Chothia also studied the conformations of antigen-binding sites of immunoglobulins. They discovered the “canonical-structure model” for the conformation of the complementarity-determining regions of antibodies, and they applied this model to the analysis of antibody-germ-line genes, including the prediction of the structure of the corresponding proteins. This work has supported the “humanization” of antibodies for therapy in the treatment of cancer. “This approach to cancer therapy is based on the observation of H. Waldmann that rats can raise antibodies against human cancers, but that the rat antibodies lead to immune responses, similar to allergies, in human patients,” Lesk explains. “Humanization of these antibodies is the formation of hybrid molecules that are more human than rat, but that retain the therapeutic activity while reducing the patient’s immune response.”
Lesk’s work also involves the detailed comparison of proteins in different structural states as a means for understanding the mechanisms that enable the proteins to change conformation, both as part of their normal activity and in disease. The discovery and analysis of these mechanisms was the key to understanding conformation changes in serine protease inhibitors, also known as serpins, mutations of which are an important cause of several diseases, including emphysema and certain types of inherited mental illness.
Lesk used a systematic analysis of protein-folding patterns to develop a mathematical representation that aids in the recognition and classification of these patterns. He also wrote the first computer program to generate schematic diagrams of proteins using molecular graphics, and he developed many algorithms now used by other researchers to analyze the structures of proteins.
Lesk was formerly chair of the Task Group on Biological Macromolecules for the Committee on Data for Science and Technology (CODATA), which aimed to foster worldwide coordination of databases in molecular biology to enhance their quality and utility. He has given invited lectures and presentations related to his research at universities and professional conferences worldwide.
Lesk is a member of the American Physical Society. He has published 189 scientific articles and 8 books related to his research.
Prior to joining Penn State during the fall semester of 2003, Lesk was on the faculty of the clinical school at the University of Cambridge from 1990 to 2003. He was a group leader in the biocomputing program at the European Molecular Biology Laboratory in Heidelberg, Germany, from 1987 to 1990; a visiting scientist at MRC Laboratory of Molecular Biology in Cambridge, United Kingdom, between 1977 and 1990; and a professor of chemistry at Fairleigh Dickinson University in New Jersey from 1971 to 1987. He has held visiting fellowships at the University of Otago in New Zealand and Monash University in Australia. He also is a Life Member of Clare Hall at the University of Cambridge in the United Kingdom.
Along with Karl D. Hardman, Lesk wrote the first computer program for generating the schematic diagram of protein structure. It is known to produce one of the most effective representations of the protein structures and employs the classification scheme for Ribbon Diagrams created by Jane Richardson. Although these schematic diagrams are less detailed compared to the other representations, such as, picture stimulating wire models or space-filling models, it is more effective in presenting the topological relationships among elements of secondary structure and protein, due to its simplistic structural expression. This was then further improved by creating a program to produce stereoscopic pairs of diagrams. As a result, the viewer’s ability to perceive spatial relationship in complex molecules was enhanced.
Operation of the program
The basic operation of the program begins with the execution of line drawing. There are four phases involved in this program:
Arthur Lesk's son, Victor Lesk has followed his father into the field of structural biology / bioinformatics, and is currently holds a post-doctoral research position with Michael Sternberg at Imperial College London.
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Arthur_M._Lesk". A list of authors is available in Wikipedia.|