Yuk Y. Sham, PhD

Assistant Professor, Department of Integrative Biology and Physiology (IBP)

Yuk Y. Sham

Contact Info


Office Phone 612-625-6255

Fax 612-625-5149

Office Address:
3-137 CCRB
2231 6th St. SE
Minneapolis, MN 55455

Mailing Address:
Cancer & Cardiovascular Research Building
2231 6th St. SE
Minneapolis, MN 55455

Lab Address:
3-210 CCRB
644 21st Avenue SE
Minneapolis, MN 55455

Post Doctoral Fellowship, IBM, 2002

Post Doctoral Fellowship, National Cancer Institute, 2000

PhD, University of Southern California (Chemistry), 1999

BS, Florida International University (Chemistry), 1994


Research Summary/Interests

My laboratory focus on the development of consistent and accurate computational models to understand the fundamental forces that governs the biomolecular recognition process. These models serves as the platform for understanding binding selectivity and structure-based drug discovery. We work collaboratively with researchers across the University to develop novel cardiovascular, antiviral, antibacterial and anticancer therapies.


PUBMED Link to Publications

  • Discovery of Aminoglycosides as first in class, nanomolar inhibitors of Heptosyltransferase I. Scientific Reports (Mnior revision). Milicaj J, Hassan BA, Cote JM, Ramirez-Mondragon C, Jaunbocus NA, Rafalowski AA, Patel KR, Castro CD, Muthyala R, Sham YY, Taylor EA. bioRxiv 2021.10.03.462930; doi: https://doi.org/10.1101/2021.10.03.462930.
  • Facile and Adaptable Synthesis of a Prazosin Analogue Library: Bringing Medicinal Chemistry into the Undergraduate Curriculum. Milicaj J, Dodda VR, Patel KR, Aragon IR, O’Connell T, Muthyala R, Taylor EA, Sham YY. Journal of Chemical Education 99: 1428-1434 (2022).
  • Ligand induced conformational and dynamical changes in a GT-B glycosyltransferase: Molecular dynamic Simulations of heptosyltransferase I complexes. Hassan BA, Milizaj J., Ramirez-Mondragon C, Sham YY, Taylor EA. Journal of Chemical Information and Modeling, 62:324–339 (2022). PMID: 34967618.
  • The molecular identity of the TLQP-21 peptide receptor. Sahu B, Nguyen ME, Rodriguez P, Pallas, JP, Ghosh V, Razzoli M, Sham YY, Salton SR, Bartolomucci A. Cellular and Molecular Life Sciences, 78(23):7133-7144. (2021) PMID: 34626205.
  • Fragment based screening and hit-based substructure search: Rapid discovery of 8-hydroxyquinonline-7-carboxylic acid as a low-cytotoxic, nanomolar metallo b-lactamase inhibitor. Shin WS, Bergstrom A, Crowder MW, Muthyala R, Sham YY. Chemical Biology and Drug Design, 98(4):481-492 (2021). PMID: 34148302.
  • Conserved conformational hierarchy across functionally divergent glycosyltransferases of the GT-B structural superfamily as determined from microsecond molecular dynamics. Ramirez-Mondragon CA, Nguyen ME, Milizaj J, Hasan B, Tucci FJ, Muthyala R, Gao J, Taylor EA, Sham YY. International Journal of Molecular Sciences, 22(9):4619 (2021). PMID: 33924837.
  • CD200 immune checkpoint reversal at the site of tumor vaccine inoculation: A novel approach to glioblastoma immunotherapy. Xiong Z, Ampudia-Mesias E, Pluhar GE, Rathe SK, Largaespada DA, Sham YY, Moertel CL, Olin MRClinical Cancer Research, 26: 232-241 (2020). PMID: 31624103.

  • Opposites attract: Escherichia coli HepI changes induced by substrate - positively charged residue interactions. Cote JM, Hecht CJS, Patel K, Ramirez-Mondragon CA, Sham YY, Taylor EA Biochemistry, 59:3135-3147 (2020). PMID: 32011131.
  • Peptide / receptor coevolution explains the lipolytic function of the neuropeptide TLQP-21.  Sahu BS, Han R, Cero C, Razzoli M, Rodriguez P, Nguyen ME, Piaggi P, Pavlicev M, Muglia L, Mahata S, O’Grady S, Baier L, Sham YY, Bartolomucci A Cell Report, 28:2567-2580 (2019). PMID: 31484069.
  • Modeling and Simulation of hGAT1: A Mechanistic Investigation of the GABA Transport Process. Zafar S, Nguyen ME, Muthyala R, Jabeen I, Sham YY Computational and Structural Biotechnology Journal,17:61-69 (2019). PMID: 30619541.
  • DNA methyltransferase activity in the presence of oxidized forms of 5-methylcytosine: Structural basis for TET-mediated DNA demethylation. Seiler CL, Fernandez J, Koerperich Z, Anderson MP, Kotandeniya D, Nguyen ME, Sham YY, Tretyakova N Biochemistry 57:6061-6069 (2018). PMID: 30230311.
  • Muscle membrane integrity in Duchenne Muscular Dystrophy: recent advances in copolymer-based muscle membrane stabilizers. Houang EM, Sham YY, Bates FS, Metzger JMSkeletal Muscle, 8:31 (2018).
  • An indole-chalcone inhibits multidrug-resistant cancer cell growth by targeting microtubules, Cong H, Zhao X, Castle BT, Pomeroy EJ, Zhou B, Lee J, Wang Y, Bian T, Miao Z, Zhang W, Sham YY, Odde DJ, Eckfeldt CE, Xing C, Zhuang C, Molecular Pharmaceutics, 15:3892-3900 (2018). PMID: 30048137.
  • The TnI structural interface with the N-terminal lobe of TnC as a determinant of cardiac contractility, Vetter A, Houang EM, Sell JJ, Thompson BR, Sham YY, Metzger JM, Biophysical Journal, 114:1646-1656 (2018). PMID: 29642034.
  • Can 5-methylcytosine analogues with extended alkyl side chain guide DNA methylation? Kotandeniva D, Seiler CL, Fernandez J, Curwick L, Pujari SS, Murphy K, Wickramaratne S, Yan S, Murphy D, Sham YY, Tretyakova NY, Chemical Communication, 54:1061-1064 (2018). PMID: 29323674.
  • Aptamer adaptive binding assessed by stilbene photoisomerization towards reversible aptasensors. Zhou Y, Wu Y, Pokholenko O, Grimsrud M, Sham Y, Papper V, Marks R, Steele T. Sensors and Actuators: B: Chemical, 257: 245–255 (2018).
  • All-atom molecular dynamics-based analysis of membrane stabilizing copolymer interactions with lipid bilayers probed under constant surface tensions. Houang EM, Bates FS, Sham YY, Metzger JM. Journal of Physical Chemistry B, 121:10657-10664 (2017). PMID: 29049887.
  • Discovery of 1-hydroxypyridine-2(1H)-thiones-6-carboxylic acid as a low cytotoxic nanomolar broadspectrum metallo beta-lactamase inhibitor. Shin WS, Bergstrom A, Xie J, Bonomo RA, Crowder MW, Muthyala R, Sham YY ChemMedChem, 12: 845–849 (2017).
  • Endgroup modified diblock copolymers inform anchor and chain mechanism of membrane stabilization. Houang EM, Haman KJ, Kim M, Zhang W, Lowe DA, Sham YY, Lodge TP, Hackel BJ, Bates FS, Metzger JM. Molecular Pharmaceutics, 14: 2333–2339 (2017).
  • The Stories Tryptophans Tell: Exploring Protein Dynamics of Heptosyltransferase I from Escherichia coli. Cote JM, Ramirez-Mondragon CA, Siegel ZS, Czyzyk DJ, Gao J, Sham YY, Mukerji I, Taylor EA. Biochemistry, 56:886-895 (2017).
  • Bypass of DNA-Protein Cross-links Conjugated to the 7-Deazaguanine Position of DNA by Translesion Synthesis Polymerases. Wickramaratne S, Ji S, Mukherjee S, Su Y, Pence MG, Lior-Hoffmann L, Fu I, Broyde S, Guengerich FP, Distefano M, Schärer OD, Sham YY, Tretyakova N. J Biol Chem, 291:23589-23603 (2016).
  • Mosquito salivary allergen Aed a 3: cloning, comprehensive molecular analysis, and clinical evaluation. Peng Z, Xu WW, Sham Y, Lam H, Sun D, Cheng L, Rasic NF, Guan Q, James AA, Simons FE. Allergy, 71:621-628 (2016).
  • Inhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor/Chemokine Receptor5 Heteromer (MOR-CCR5). Akgün E, Javed MI, Lunzer MM, Powers MD, Sham YY, Watanabe Y, Portoghese PS. J Med Chem, 58: 8647-57 (2015).
  • Discovery of 1-hydroxypyridine-2-thiones as selective histone deacetylase inhibitors and their potential application for treating leukemia. Muthyala R, Shin WS, Xie J, Sham YY. Bioorg Med Chem Lett. 2015 Oct 1; 25(19): 4320-4.
  • A novel drug discovery strategy: Mechanistic investigation of an enantiomeric antitumor agent targeting dual p53 and NF-?B pathways. Zhuang C, Shin WS, Wu Y, Li J, Yao J, Sheng C, Sham YY, Miao Z, Zhang W Oncotarget, 5: 10830-10839 (2014). Abstract
  • Molecular determinants of cardiac myocyte performance as conferred by isoform-specific TnI residues Thompson BR, Houang EM, Sham YY, Metzger JM. Biophysical Journal, 106: 2105-2114 (2014).
  • Cell permeable vanX inhibitors as vancomycin re-sensitizing agents. Muthyala R, Rastogi N, Shin WS, Peterson ML, Sham YY. Bioorganic & Medicinal Chemistry Letters, 24: 2535-2538 (2014).
  • Rapid identification of small molecule inhibitors of Keap1–Nrf2 interaction through structure–based virtual screening and hit–based similarity search. Zhuang C, Narayanapillai S, Zhang W, Sham YY, Xing C. Journal of Medicinal Chemistry,57:1121-1126 (2014).
  • The amino terminus of herpes simplex virus type 1 gL is important for cell-cell fusion but not for gH trafficking. Zhou W, Chen F, Klyachkin K, Sham YY, Geraghty R J. Journal of Virology, 88:739-744 (2014).
  • Consistent pKa calculation in proteins. Chen F, Shin WS, Yoon HW, Sham YY. A course on biomolecular simulations, Villà-Freixa J, Ed., Huygens Editorial, Barcelona, Spain. (accepted).
  • Structure and stability of human telomeric G-quadruplex with preclinical 9-amino acridines. Ferreira R, Artali R, Benoit A, Gargallo R, Eritja R, Ferguson DM, Sham YY, Mazzini S. Plos One, 8: e57701 (2013).
  • 42.5-Arylidenethioxothiazolidinones as inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp1). Sirivolu VR, Vernekar S, Marchand C, Naumova A, Chergui A, Renaud A, Steven AG, Chen F, Sham YY, Pommier Y, Wang Z. Journal of Medicinal Chemistry, 55: 8671-84 (2012).
  • pH-Responsive titratable performance of histidine-modified cardiac troponin I. Palpant NJ, Houang EM, Sham YY, Metzger JM. Biophysical Journal, 102: 1570-1579 (2012).
  • The design, synthesis and biological evaluations of C-6 or C-7 substituted 2-hydroxylisoquinoline-1,3-diones as inhibitors of hepatitis C virus. Chen YL, Tang J, Kesler MJ, Sham YY, Vince R, Geraghty RJ and Wang Z. Bioorganic and Medicinal Chemistry, 20: 467–479 (2012).
  • pH-Dependent transport of pemetrexed by breast cancer resistance protein, Li l, Sham YY, Bikadi Z, Elmquist WF, Drug Metabolism and Disposition, 39: 1478-1485 (2011). (Cover Article)
  • A continuous fluorescence displacement assay for BioA: An enzyme involved in biotin. Wilson DJ, Shi C, Duckworth BP, Muretta JM, Manjunatha U, Sham YY, Thomas DD, Aldrich CC. Analytical Biochemistry, 416: 27-38 (2011). Abstract
  • 6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase. Tang J, Maddali K, Dreis CD, Sham YY, Vince R, Pommier Y, Wang Z. Bioorganic & Medicinal Chemistry Letters, 21:2400-2402 (2011). Abstract
  • 3-Hyroxypyrimidine-2,4-diones as novel scaffold for HIV integrase inhibitor design. Tang J, Maddali K, Metifiot M, Sham YY, Vince R, Pommier Y, Wang Z. Journal of Medicinal Chemistry, 54:2282-92 (2011). 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
  • Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylase based on a cinnamic hydroxamic acid core structure. Chen L, Petrelli R, Gao G, Wilson D, McLean GT, Jayaram HN, Sham YY, Pankiewicz KW. Bioorganic and Medicinal Chemistry 18: 5950-5964 (2010). Abstract
  • Triazole-linked inhibitors of inosine monophosphate dehydrogenase from human andMycobacterium tuberculosis. Chen L, Wilson DJ, Xu Y, Aldrich CC, Felczak K, Sham YY, Pankiewicz KW. Journal of Medicinal Chemistry 53: 4768-4778 (2010). PMID: 20491506. 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). PMID: 20423961. 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). PMID: 20457521. Abstract
  • Design, asymmetric synthesis and evaluation of pseudosymmetric sulfoximine inhibitors against HIV-1 protease. Lu D, Sham YY, Vince R. Bioorganic and Medicinal Chemistry 18: 2037-2048 (2010). PMID: 20138769. Abstract
  • Selective inhibition of NAD kinases by dinucleoside disulfide NAD mimics. Petrelli R, Sham YY, Chen L, Felczak K, Bennett E, Wilson D, Aldrich C, Yu JS, Cappellacci L, Franchetti P, Grifantini M, Mazzola F, Di Stefano M, Magni G, Pankiewicz K. Bioorganic and Medicinal Chemistry 17: 5656-5664 (2009). PMID: 19596199. 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). PMID: 19361422. Abstract
  • Design and synthesis of asymmetric sulfoximine inhibitors for HIV-1 protease. Raza A, Sham YY, Vince R. Bioorganic and Medicinal Chemistry Letters 18: 5406-5410 (2008). PMID: 18829317. Abstract
  • CXC and CC-chemokines form mixed heterodimers: Association free energies from MD simulations and experimental correlations. Nesmelova IV, Sham YY, Gao J, Mayo KH. Journal of Biological Chemistry 283: 24155-24166 (2008). PMID: 18550532. Abstract
  • Impact of the C terminal loop of histidine triad nucleotide binding protein1 (Hint1) on substrate specificity. Chou TF, Sham YY, Wagner CR. Biochemistry 46: 13074-79 (2007). PMID: 17939685. Abstract
  • A universal method for the preparation of covalent protein DNA conjugates for use in creating protein nanostructures. Duckworth BP, Chen Y, Wollack JW, Sham YY, Mueller JD, Taton TA, Distefano MD. Angewandte Chemie International Edition 46: 8819-8822 (2007). PMID: 17935099. Abstract
  • Direct inhibition of insulin-like growth factor-I receptor kinase activity by (-)-epigallocatechin-3-gallate regulates cell transformation. Li M, He Z, Ermakova S, Zheng D, Tang F, Cho YY, Zhu F, Ma WY, Sham YY, Rogozin EA, Bode AM, Cao Y, Dong Z. Cancer Epidemiology Biomarkers Prevention 16: 598-605 (2007). PMID: 17372258. 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). PMID: 17227711. 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: 35-44 (2007). PMID: 17148476. Abstract
  • Amiodarone analog dependent effects on CYP2C9 mediated metabolism and kinetic profiles. Kumar V, Locuson CW, Sham YY, Tracy TS. Drug Metabolism and Disposition 34: 1688-96 (2006). PMID: 16815961. 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). PMID: 15776407. Abstract
  • Platelet factor 4 and interleukin-8 CXC chemokine heterodimer formation modulates function at the quaternary structural level. Nesmelova IV, Sham YY, Dudek AZ, Slungaard A, Mayo KH. Journal of Biological Chemistry 280: 4948-4958 (2005). PMID: 15531763. 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 YY, Suits F, Swope W, Ward JJ C, Zhestkov Y, Zhou R, Journal of Parallel and Distributed Computing 63: 759-773 (2003). Abstract
  • Critical building blocks in proteins: A common theme on folding and function. Kumar S, Barzilai A, Haspel N, Sham YY, Tsai CJ, Wolfson HJ, Nussinov R. Recent research developments in protein folding, stability and design, Gromiha MM and Selvaraj S, Eds., Research Signpost, Trivandrum, India. 207-217 (2002). 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). PMID: 11835506. Abstract
  • Case study: An environment for understanding protein simulations using game graphics. Gresh D, Suits F, Sham YY. Proceedings of IEEE Visualization 445-448 (2001). Abstract
  • Structured disorder and conformational selection. Tsai CJ, Ma B, Sham YY, Kumar S, Nussinov R. Proteins: Structure, Function, and Bioinformatics 44: 418-427 (2001). PMID: 11484219. Abstract
  • A hierarchical, building blocks based computational method for protein structure prediction. Tsai C J, Ma B, Sham YY, Kumar S, Wolfson H, Nussinov R. IBM Journal of Research and Development 45: 513-23 (2001). Abstract
  • Blue Gene: A vision for protein science using a petaflop supercomputer. Allen F, Almasi G, Andreoni W, Beece D, Berne B J, Bright T, Brunheroto J, Cascaval C, Castanos J, Coteus P, Crumley P, Curioni A, Denneau M, Donath W, Eleftheriou M, Fitch B, Fleischer B, Georgious C J, Germain R, Giampapa M, Gresh D, Gupta M, Haring R, Ho H, Horchschild P, Hummel S, Jonas T, Lieber D, Martyna G, Maturu K, Moreira J, Newns D, Newton M, Philhower R, Picunko T, Pitera J, Pitman M, Rand R, Royyuru A, Salapura V, Sanomiya A, Shah R, Sham Y, Singh S, Snir M, Suits F, Swetz R, Swope W C, Vishnumurthy N, Ward T J C, Warren H, Zhou R. IBM Systems Journal 40: 310-27 (2001). Abstract
  • Protein folding and function: The N terminal fragment in adenylate kinase. Kumar S, Sham YY, Tsai CJ, Nussinov R. Biophysical Journal 80: 2439-54 (2001). PMID: 11325743. Abstract
  • Molecular dynamic simulation of Escherichia coli dihydrofolate reductase and its protein fragments: Relative stability of protein fragments in experiment and simulations. Sham YY, Ma B, Tsai CJ, Nussinov R. Protein Science 10: 135-48 (2001) (Cover article). PMID: 11266602. Abstract
  • How important are entropic contributions to enzyme catalysis?J, Strajbl M, Glennon TM, Sham YY, Chu ZT, Warshel A. Proceedings of the National Academy of Sciences 97: 11899-904 (2000). PMID: 11050223. 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 ZT, Warshel A. Proteins: Structure, Function, and Bioinformatics 39: 393-407 (2000). ). PMID: 10813821. Abstract
  • Calculations of activation entropies of chemical reactions in solution. Strajbl S, Sham YY, Villà J, Chu ZT, Warshel A.. Journal of Physical Chemistry B 104: 4578-4584 (2000). Abstract
  • Simulating proton translocation in proteins: Probing the proton transfer pathways in the Rhodobacter sphaeroides Reaction Center. Sham YY, Muegge I, Warshel A. Protein: Structure, Function, and Bioinformatics 36: 484-500 (1999). PMID: 10450091. Abstract
  • The surface constraint all atom model provides size independent results in calculations of hydration free energies. Sham YY, Warshel A. Journal of Chemical Physics 109: 7940-7944 (1998). 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). PMID: 9545037. Abstract
  • 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
  • Temperature dependent near UV molar absorptivities of several small aldehydes in aqueous solution. Sham YY, Joens JA. Spectrochimica Acta A 51: 247-51 (1995). Abstract