Vikram Mulligan

Vikram K. Mulligan, PhD

About Me:

University of Toronto, Hon. B.Sc. in Biochemistry (specialist), Physics (major)

University of Toronto, Ph.D. in Biochemistry

vmullig@uw.edu


My primary research focus is the development of computational techniques for designing folding, protein-like heteropolymers synthesized from non-natural building blocks. Rationally-designed, folding heteropolymers could be used as a new class of therapeutic agents to treat disease, or as exotic new nanomaterials. I am applying my methods to the creation of rigidly-structured macrocycle inhibitors of enzymes involved in antibiotic resistance, and to other difficult problems in human health.


Publications:

*Hosseinzadeh P, *Bhardwaj G, *Mulligan VK, Shortridge MD, Craven TW, Pardo-Avila F, Rettie SA, Kim DE, Silva D-A, Ibrahim YM, Webb IK, Cort JR, Adkins JN, Varani G, Baker D. (2017). Comprehensive computational design of ordered peptide macrocycles. Science. In press. (Note: P Hosseinzadeh, G Bhardwaj, and VK Mulligan contributed equally to this work.)

*Dang B, *Wu H, *Mulligan VK, Mravic M, Wu Y, Lemmin T, Ford A, Silva D-A, Baker D, DeGrado WF. (2017). De novo design of covalently constrained mesosize protein scaffolds with unique tertiary structures. Proc. Natl. Acad. Sci. USA. 114(41):10852-7. (*Note: B Dang, H Wu, and VK Mulligan contributed equally to this work.)

Rocklin GJ, Chidyausiku TM, Goreshnik I, Ford A, Houliston S, Lemak A, Carter L, Ravichandran R, Mulligan VK, Chevalier A, Arrowsmith CH, Baker D. (2017). Global analysis of protein folding using massively parallel design, synthesis, and testing. Science 357(6347):168-75.

Alford RF, Leaver-Fay A, Jeliazkov JR, O’Meara MJ, DiMaio FP, Park H, Shapovalov MV, Renfrew PD, Mulligan VK, Kappel K, Labonte JW, Pacella MS, Bonneau R, Bradley P, Dunbrack RL Jr, Das R, Baker D, Kuhlman B, Kortemme T, Gray JJ. (2017). The Rosetta all-atom energy function for macromolecular Modeling and design. J. Chem. Theory Comput. 13(6):3031-48.

Park H, Bradley P, Greisen P Jr, Liu Y, Mulligan VK, Kim DE, Baker D, DiMaio F. (2017). Simultaneous Optimization of Biomolecular Energy Functions on Features from Small Molecules and Macromolecules. J. Chem. Theory Comput. 12(12):6201-12.

*Bhardwaj G, *Mulligan VK, *Bahl CD, Gilmore JM, Harvey PJ, Cheneval O, Buchko GW, Pulavarti SV, Kaas Q, Eletsky A, Huang PS, Johnsen WA, Greisen PJ, Rocklin GJ, Song Y, Linsky TW, Watkins A, Rettie SA, Xu X, Carter LP, Bonneau R, Olson JM, Coutsias E, Correnti CE, Szyperski T, Craik DJ, Baker D. (2016). Accurate de novo design of hyperstable constrained peptides. Nature 538(7625):329-35. (*Note: G Bhardwaj, VK Mulligan, and CD Bahl contributed equally to this work.)

Mills JH, Khare SD, Bolduc JM, Forouhar F, Mulligan VK, Lew S, Seetharaman J, Tong L, Stoddard BL, Baker D. (2013). Computational design of an unnatural amino acid dependent metalloprotein with atomic level accuracy. J. Am. Chem. Soc. 135(36):13393-9.

Mulligan VK, Chakrabartty A. (2013). Protein misfolding in the late-onset neurodegenerative diseases: common themes and the unique case of amyotrophic lateral sclerosis. Proteins 81(8):1285-303.

Mulligan VK, Kerman A, Laister RC, Sharda PR, Arslan PE, Chakrabartty A. (2012). Early steps in oxidation-induced SOD1 misfolding: implications for non-amyloid protein aggregation in familial ALS. J. Mol. Biol. 421(4-5):631-52.

Mulligan VK, Hadley KC, Chakrabartty A. (2012). Analyzing complicated protein folding kinetics rapidly by analytical Laplace inversion using a Tikhonov regularization variant. Anal. Biochem. 421(1):181-90.

Ceccarelli DF, Laister RC, Mulligan VK, Kean MJ, Goudreault M, Scott IC, Derry WB, Chakrabartty A, Gingras AC, Sicheri F. (2011). CCM3/PDCD10 heterodimerizes with germinal center kinase III (GCKIII) proteins using a mechanism analogous to CCM3 homodimerization. J. Biol. Chem. 286(28):25056-64.

Ip P, Mulligan VK, Chakrabartty A. (2011). ALS-causing SOD1 mutations promote production of copper-deficient misfolded species. J. Mol. Biol. 409(5):839-52.

Khan MQ, Sweeting B, Mulligan VK, Arslan PE, Cashman NR, Pai EF, Chakrabartty A. (2010). Prion disease susceptibility is affected by beta-structure folding propensity and local side-chain interactions in PrP. Proc Natl Acad Sci U.S.A. 107(46):19808-13.

Arslan PE, Mulligan VK, Ho S, Chakrabartty A. (2010). Conversion of Abeta42 into a folded soluble native-like protein using a semi-random library of amphipathic helices. J. Mol. Biol. 396(5):1284-94.

Mulligan VK, Kerman A, Ho S, Chakrabartty A. (2008). Denaturational stress induces formation of zinc-deficient monomers of Cu,Zn superoxide dismutase: implications for pathogenesis in amyotrophic lateral sclerosis. J. Mol. Biol. 383(2):424-36.

D’Alterio C, Tran DD, Yeung MW, Hwang MS, Li MA, Arana CJ, Mulligan VK, Kubesh M, Sharma P, Chase M, Tepass U, Godt D. (2005). Drosophila melanogaster Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli. J. Cell Biol. 171(3):549-58.