Yuk Sham, Ph.D.

Assistant Professor, Center for Drug Design
Assistant Director, Center for Drug Design

Contact information

Office: 7-220 Phillips Wangensteen
Phone: 612-625-8255
Fax: 612-625-8154
E-mail: shamx002@umn.edu
Research Page: http://azt.cdd.umn.edu

Education

B.S., Florida International University, 1994
Ph.D., University of Southern California, 1999
Post Doc, National Cancer Institute, 1999-2000
Post Doc, IBM, 2001-2002

Research Summary

Many of the diseases today can be treated by the inhibition of protein targets that play an essential role in the life cycle for a virus, bacteria or cancer cells. I am interested in developing consistent and accurate computational approaches to study the energy, structure and function relationships of biomolecular systems and their applications to therapeutic discovery. Our goal is to understand the molecular recognition process which plays a critical role in the cellular signaling processes and enzyme catalysis. Particularly, I am focused in studying the protein-protein and protein-substrate interactions. Ability to quantify analytically these interactions will provide us with an insight on how these therapeutic targets selectively bind as well as a rational basis to structure based drug design. In collaboration with other members of CDD, we are currently working on protein targets that are important for the treatment of AIDS, tuberculosis and cancer.

Selected Publication

Consistent calculations of pKa's of ionizable residues in proteins: semi microscopic and microscopic approaches. Sham YY, Chu ZT, Warshel A. Journal of Physical Chemistry B 1997, 101(22): 4458-72.  Abstract

The effect of protein relaxation on charge-charge interactions and dielectric constants in proteins. Sham YY, Muegge I, Warshel A. Biophysical Journal 1998, 74(4): 1744-53. Abstract

Examining methods for calculations of binding free energies: LRA, LIE, PDLD LRA and PDLD/S LRA calculations of ligand binding to HIV protease. Sham YY, Tao H, Chu Z T and Warshel A. Proteins: Structure, Function, and Bioinformatics 2000, 39(4): 393-407. Abstract

How important are entropic contributions to enzyme catalysis? Villà J, Strajbl M, Glennon TM, Sham YY, Chu ZT, Warshel A. Proceedings of the National Academy of Sciences 2000, 97(22): 11899-904. Abstract

Thermal unfolding molecular dynamic simulation of Escherichia Coli Dihydrofolate reductase: thermal stability of protein domains and unfolding pathway. Sham YY, Ma B, Tsai CJ, Nussinov R. Proteins: Structure, Function, and Bioinformatics 2002, 46(3): 308-20. Abstract

Blue Matter, An application framework for molecular simulation on Blue Gene. Fitch BG, Germain RS, Mendell M, Pitera J, Pitman M, Rayshubskiy A, Sham Y, Suits F, Swope W, Ward JJ C, Zhestkov Y, Zhou R. Journal of Parallel and Distributed Computing 2003, 63(7): 759-73. Abstract

Homology modeling and molecular dynamic simulation of mu opioid receptor in a membrane aqueous system. Zhang Y, Sham YY, Rajamani R, Gao J, Portoghese PS. ChemBioChem 2005, 6(5): 853-59. Abstract

Development of selective inhibitors for anti apoptotic Bcl 2 proteins from BHI 1. Xing C, Wang L, Tang X, Sham YY. Bioorganic and Medicinal Chemistry 2007, 15(5): 2167-76. Abstract

CXC and CC-chemokines form mixed heterodimers: Association free energies from MD simulations and experimental correlations. Nesmelova IV, Sham Y, Gao J, Mayo KH. Journal of Biological Chemistry 2008, 283(35): 24155-66. Abstract

Shared catalysis in virus entry and bacterial cell wall depolymerization. Cohen DN, Sham YY, Haugstad GD, Xiang Y, Rossmann MG, Anderson DL, Popham DL. Journal of Molecular Biology 2009, 387(3): 607-618. Abstract

Selective inhibition of NAD kinases by dinucleoside disulfide NAD mimics. Petrelli R, Sham YY, Chen L, Felczak K, Bennett EM, Aldrich C, Wilson D, Yu JS, Cappellacci L, Franchetti P, Grifantini M, Mazzola F, Di Stefano M, Magni G, Pankiewicz K. Bioorganic & Medicinal Chemistry. Bioorganic & Medicinal Chemistry 2009, 17(15): 5656-5664. Abstract