Yuk Sham, Ph.D. - AHC - Center for Drug Design, University of Minnesota

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

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

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.

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, 101:4458-4472 (1997). Abstract

The effect of protein relaxation on charge-charge interactions and dielectric constants in proteins. Sham YY, Muegge I, Warshel A. Biophysical Journal, 74:1744-1753 (1998). 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, 39:393-407 (2000). 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): 11899-11904. 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, 46:308-320 (2002). 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, 63:759-773 (2003). 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, 6:853-859 (2005). Abstract

A critical role for the loop region of the basic helix-loop-helix/leucine zipper protein Mlx in DNA binding and glucose regulated transcription. Ma L, Sham YY, Walters KJ, Towle HC Nucleic Acids Research, 35(1): 35-44 (2007). 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, 15:2167-2176 (2007). 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, 283: 24155-24166 (2008). 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, 387:607-618 (2009). Abstract

Scaffold rearrangement of dihydroxypyrimidine inhibitors of HIV integrase: Docking model revisited. Tang J, Maddali K, Pommier Y, Sham YY, Wang Z. Bioorganic and Medicinal Chemistry Letters 20: 3275-3279 (2010). Abstract

Pathogenic peptide deviations support a model of adaptive evolution of chordate cardiac performance by troponin mutation. Palpant NJ, Houang EM, Delport W, Hastings K, Onufrieve AV, Sham YY, Metzger JM. Physiological Genomics, 42: 287-299 (2010). Abstract

Triazole-linked inhibitors of inosine monophosphate dehydrogenase from human and Mycobacterium tuberculosis. Chen L, Wilson DJ, Xu Y, Aldrich CC, Felczak K, Sham YY, Pankiewicz KW. Journal of Medicinal Chemistry, 53: 4768-4778 (2010). Abstract

N-3 Hydroxylation of Pyrimidine-2,4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase. Tang J, Maddali K, Dreis CD, Sham YY, Vince R, Pommier Y, Wang Z. ACS Medicinal Chemistry Letters, 2: 63-67 (2011). Abstract

3-Hydroxypyrimidine-2,4-diones as an Inhibitor Scaffold of HIV Integrase. Tang J, Maddali K, Sham YY, Vince R, Pommier Y, Wang Z. Journal of Medicinal Chemistry, 2: 63-67 (2011). Abstract

The Design, Synthesis and Biological Evaluations of C-6 or C-7 Substituted 2-Hydroxyisoquinoline-1,3-diones as Inhibitors of Hepatitis C Virus. Chen YL, Tang J, Kesler M, Sham YY, Vince R, Geraghty RJ, Wang Z, Bioorganic and Medicinal Chemistry, 20:467-479 (2012). Abstract