VIKAS NANDA

 

Associate Professor of Biochemistry and Molecular Biology
Robert Wood Johnson Medical School - Rutgers University 

Resident Faculty Member




Laboratory of Computational Design and Molecular Evolution of Proteins


Research  Publications  Current Members Funding  Contact


Research


Our group is interested in constructing new proteins for applications in biomedical research, nanotechnology and as tools for understanding how proteins fold and evolve. Significant progress has been made in the last decade using sophisticated computer programs to design proteins with novel folds and functions. We maintain and develop software for protein design, structure prediction and docking of protein-ligand complexes. Several design projects our group pursues include the computational design of an extracellular matrix, thermostabilization of peptide therapeutics with D-amino acids and prediction of allergenicity of food proteins.

Design of a Synthetic Matrix - The extracellular matrix (ECM) is a complex network of collagens, laminins, fibronectins and proteoglycans that provides a surface upon which cells can adhere, differentiate and proliferate. Defects in the ECM are the underlying cause of a wide spectrum of diseases. The ECM mediates endothelial cell polarity and under normal conditions can suppress pre-oncogenic transitions to a neoplastic state. We are constructing artificial, de novo collagen-based matrices using a hierarchic computational approach. These matrices are physically characterized in the laboratory and used to probe the role of chemical and spatial organization in the ECM on the tumor forming potential of adhered cells.

Design of Peptide Therapeutics - Peptides are an emergent and important class of therapeutics with over forty compounds on the market and nearly 700 more in clinical or pre-clinical trials. During the development of peptide drugs, D-enantiomers of amino acids are frequently incorporated to improve pharmacokinetic and pharmacodynamic properties by lowering susceptibility to proteolysis. Typically, such modifications are introduced in lead compounds by trial-and-error or combinatorial approaches. Our laboratory is developing software to simulate the impact of non-natural amino acids on structure and stability. Using fundamental principles of protein design, we will pursue the computational, structure-based development of peptides with variable chirality, broadly extending our capacity to create safe and potent therapeutics.


Food Allergy - A crucial and unanswered question in the field of food allergy research is why certain proteins elicit an IgE mediated immune response, while others are tolerated. One compelling hypothesis is that non-allergens are more digestible, resulting in sufficient protein degradation in the stomach and intestine to render the remaining fragments immunologically inert. Despite efforts to contrast the proteolytic stability of allergens and non-allergens, a clear link between digestibility and allergenicity has yet to be established. Confounding variables such as interactions with other components in the food matrix, cross-reactivity with other allergens, or the pathway of sensitization (e.g. alimentary canal versus respiratory tract) complicate the interpretation of experimental outcomes. We are developing a highly defined system for exploring the relationship between digestibility and allergenicity. We hypothesize that the digestibility of a protein is dependent on its stability under acidic (pH less than 3.0) conditions. Using shrimp tropomyosin as a model system, we will computationally design acid sensitive variants that are rapidly proteolyzed in gastric fluid. These mutants will provide optimal reagents for comparative studies relating pH-stability to digestibility and eventually to allergenicity.





Publications



    2017


  1. Belure, S., Shir, O.M., Nanda, V. Protein Design by Multiobjective Optimization:  Evolutionary and Non-Evolutionary Approaches. Proceedings of the Genetic and Evolutionary Computation Conference (GECCO-2017), ACM Press (in press)

  2. Li BI, Ababon MR, Matteson PG, Lin Y, Nanda V, Millonig JH. Congenital Cataract in Gpr161vl/vl Mice Is Modified by Proximal Chromosome 15. PLoS ONE 2017; 12(1): e0170724.


  3. Cai, N., Bai, Z., Nanda, V., Runnels, L.W. Mass Spectrometric Analysis of TRPM6 and TRPM7 Phosphorylation Reveals Regulatory Mechanisms of the Channel-Kinases. Sci. Rep. 2017 7:42739


  4. 2016

  5. Drzewiecki, K.E., Grisham, D.R., Parmar, A.V., Nanda, V., Shreiber, D.I. Circular Dichroism Spectroscopy of Collagen Fibrillogenesis:  A New Use for an Old Technique. Biophys. J. 2016; 111(11): 2377-2386.


  6. Nanda, V.  Heterogeneous Epitaxy:  Peptides Scale Graphene's Surface.  Biophys. J. 2016; 110(11):  2291-2.


  7. Maeda, Y., Ikezoe, Y., Pike, D.H., Nanda, V., Matsui, H.  Molecular self-assembly strategy for generating catalytic hybrid peptides.  PLoS ONE. 2016 11(4): e0153700.
    http://dx.doi.org/10.1371/journal.pone.0153700

  8. Parmar, A.S.*, James, J.K.*, Grisham, D.R., Pike, D.H., Nanda, V.  Dissecting electrostatic contributions to folding and self-assembly using designed multicomponent peptide systems. J. Amer. Chem. Soc. 2016; 138(13):  4362-67. *contributed equally dx.doi.org/10.1021/jacs.5b10304

  9. Nanda, V., Senn, S., Pike, D.H., Rodriguez-Granillo, A., Hansen, W., Khare, S.D., Noy, D.  Structural principles for computational and de novo design of 4Fe-4S metalloproteins.  BBA Bioenergetics. 2016; 1857(5):  531-8.
    http://dx.doi.org/10.1016/j.bbabio.2015.10.001

  10. Nanda, V.  Getting to the bottom of the TIM barrel.  Nature Chem Bio. 2016; 12(1): 2-3.
    http://dx.doi.org/10.1038/nchembio.1987


  11. 2015


  12. Parmar, A.S., Xu, F., Pike, D.H., Belure, S., Hasan, N., Drzewiecki, K.E., Shreiber, D.I., Nanda, V.  Metal stabilization of collagen and de novo designed mimetic peptides. Biochemistry. 2015; 54(32): 4987–4997.
    https://sites.google.com/site/viknanda/home/bi-2015-00502p_0012.gif?attredirects=0
      

  13. Stapleton, J.A., Whitehead, T.A., Nanda, V.  Computational redesign of the lipid-facing surface of the outer membrane protein OmpA.  Proc. Natl. Acad. Sci. 2015; 112(31):  9632-7.
  14. https://sites.google.com/site/viknanda/home/F1.medium.gif?attredirects=0

  15. Pike, D.H., Nanda, V.  Empirical evaluation of local dielectric constants:  toward atomistic design of collagen mimetic peptides.  Biopolymers - Peptide Science. 2015; 104(4): 360-70.  Special issue in honor of Bill DeGrado on the occasion of his 60th birthday.
  16. https://sites.google.com/site/viknanda/home/bip22644-fig-0004.png

  17. Li, B.I., Matteson, P.G., Ababon, M.F., Nato, A.Q. Jr., Lin, Y., Nanda, V., Matise, T.C., Millonig, J.H.  The orphan GPCR, Gpr161, regulates the retinoic acid and canonical Wnt pathways during neurulation.  Dev. Bio. 2015; 402(1):  17-31.


  18. 2014

  19. McGuinness, K., Khan, I.J., Nanda, V.  Morphological Diversity and Polymorphism of Self-Assembling Collagen Peptides Controlled by Length of Hydrophobic Domains.  ACS Nano. 2014; 8(12):12514-23.

    https://sites.google.com/site/viknanda/home/nn-2014-05369d_0009.gif?attredirects=0

  20. Drzewiecki, K., Parmar, A.S., Gaudet, I., Branch, J., Pike, D., Nanda, V., Shreiber, D. Methacrylation Induces Rapid, Temperature Dependent, Reversible Self-Assembly of Type-I Collagen.  Langmuir.  2014; 30(37):11204-11.

    https://sites.google.com/site/viknanda/home/la-2014-02418s_0010.gif?attredirects=0

  21. Parmar, A.S., Pike, D., Nanda, V.  Computational Design of Metalloproteins.  Methods Mol. Biol. 2014; 1216:233-49.

  22. Parmar, A.S., Zahid, S., Belure, S., Young, R., Hasan, N., Nanda, V.  Design of net-charged abc-type collagen heterotrimers.  J. Struct. Biol. 2014; 185(2): 163-167.
    http://dx.doi.org/10.1016/j.jsb.2013.04.006

  23. Senn, S., Nanda, V., Falkowski, P.G., Bromberg, Y.  Function Based Assessment of Structure Similarity Measurements Using Cofactor Orientation.  Proteins:  Struct. Func. Bioinf.  2014; 82(4): 648-656.
    http://dx.doi.org/10.1002/prot.24442

  24. Huang L., Pike, D., Sleat, D.E., Nanda, V., Lobel, P.  Potential Pitfalls and Solutions for Use of Fluorescent Fusion Proteins to Study the Lysosome.  PLoS ONE. 2014; 9(2): e88893.


  25. 2013

  26. Xu, F., Khan, I.J., McGuinness, K., Parmar, A.S., Silva, T., Murthy, S., Nanda, V.  Self-Assembly of Left and Right-Handed Molecular Screws.  J. Amer. Chem. Soc. 2013; 135(50):  18762-5.
    http://dx.doi.org/10.1021/ja4106545

  27. Xu, F., Silva, T., Joshi, M., Zahid, S., Nanda, V.  Circular Permutation Directs Orthogonal Assembly in Complex Collagen Peptide Mixtures.  J. Biol. Chem. 2013; 288: 31616-23.

  28. Khan, I.J., Di, R., Patel, P., Nanda, V.  Evaluating pH-induced Gastrointestinal Aggregation of Arachis Hypogea 1 Fragments as Potential Components of Peanut Allergy.  J. Agr. Food Chem. 2013; 61(35):  8430-35.
    https://sites.google.com/site/viknanda/home/jf-2013-01701t_0006.gif?attredirects=0

  29. Nanda, V., Hsieh, D., Davis, A.  Prediction and Design of Outer Membrane Protein-Protein Interactions. Methods Mol. Biol. 2013; 1063: 183-96.

  30. Kim, J.D., Yee, N., Nanda, V., Falkowski, P.G.  Anoxic Photochemical Oxidation of Siderite Generates Molecular Hydrogen and Iron Oxides.  Proc. Natl. Acad. Sci. 2013; 110(25): 10073-77.

  31. Parmar, A.S., Joshi, M., Nosker, P.L., Hasan, N.F., Nanda, V.  Control of Collagen Stability and Heterotrimer Specificity Through Repulsive Electrostatic Interactions.  Biomolecules 2013; 3(4):  986-996.

  32. Culik, R.M., Annavarapu, S., Nanda, V., Gai, F.  Using D-amino acids to delineate the mechanism of protein folding: application to Trp-cage.  Chemical Physics. 2013; 422: 131-4.

  33. Nanda, V., Cristian, L., Toptygin, D., Brand, L., DeGrado, W.F.  Nanosecond dynamics of InfluenzaA/M2TM and an amantadine resistant mutant probed by time-dependent red shifts of a native tryptophan.  Chemical Physics 2013; 422:  73-79.
    https://sites.google.com/site/viknanda/home/1-s2.0-S0301010412004697-fx1.jpg

  34. Giddu, S., Xu, F., Nanda, V.  Sequence Recombination Improves Target Specificity in a Redesigned Collagen Peptide abc-type Heterotrimer.  Proteins:  SFB.  2013; 81(3): 386-93.


  35. 2012

  36. Hsieh, D., Nanda, V.  Dynamic surface charts for scattered 4D data in Excel spreadsheets.  Spreadsheets in Education. 2012; 6(1)

  37. Kim, J.D., Rodriguez-Granillo, A., Case, D.A., Nanda, V., Falkowski, P.G.  Energetic Selection of Topology in Ferredoxins.  PLoS Computational Biology. 2012; 8(4)

  38. Grzyb, J., Xu, F., Nanda, V., Luczkowska, R., Reijerse, E., Lubitz, W., Noy, D.  Empirical and computational design of iron-sulfur cluster proteins.  BBA - Bioenergetics.  2012; 1817:1256-62.

  39. Xu, F., Li, J., Jain, V., Tu, R., Huang, Q., Nanda, V. Compositional Control of Higher Order Assembly Using Synthetic Collagen Peptides.  J. Am. Chem. Soc. 2012; 134(1):47-50.
    https://sites.google.com/site/viknanda/home/ja-2011-077894_0007.gif?attredirects=0

  40. Hsieh, D., Davis, A., Nanda, V. A Knowledge Based Potential Highlights Unique Features of Membrane alpha-Helical and beta-Barrel Protein Insertion and Folding. Protein Science.  2012; 21(1):50-62.

  41. Stapleton, J.A., Rodriguez-Granillo, A., Nanda, V. Artificial Enzymes. In: Nanobiotechnology Handbook (Y. Xie, ed.) 2012; Taylor-Francis.


  42. 2011

  43. Xu, F.*, Zahid, S.*, Silva, T., Nanda, V. Computational Design of a Collagen A:B:C-type Heterotrimer. J. Am. Chem. Soc. 2011; 133(39):15260-3. (*contributed equally)
    http://dx.doi.org/10.1021/ja205597g

  44. Rodriguez-Granillo, A.*, Annavarapu, S.*, Zhang, L., Koder, R.L., Nanda, V. Computational Design of Thermostabilizing D-Amino Acid Substitutions. J. Am. Chem. Soc. 2011; 133(46): 18750-9. (*contributed equally)
    http://dx.doi.org/10.1021/ja205609c

  45. Nanda, V., Zahid, S., Xu, F., Levine, D. Computational Design of Intermolecular Stability and Specificity in Protein Self-AssemblyIn: Methods in Enzymology, Vol. 487 Computer Methods, Part C (M.L. Johnson and L. Brand eds.) 2011; Elsevier

  46. Rodriguez-Granillo, A., Nanda, V. Designing new enzymes with molecular simulations. Biotech International. 2011; 23: 10-13.

  47. Woronowicz, K., Sha, D. Frese, R.N., Sturgis, J.N., Nanda, V., Niederman, R.A. The effects of protein crowding in bacterial photosynthetic membranes on the flow of quinone redox species between the photochemical reaction center and the ubiquinol-cytochrome c(2) oxidoreductase. Metallomics. 2011; 3(8): 765-774.

  48. Braun, P., Goldberg, E., Negron, C., von Jan, M., Xu, F., Nanda, V., Koder, R.L., Noy, D. Design Principles for Chlorophyll Binding Sites in Helical Proteins. Proteins: SFB. 2011; 79(2): 463-476


  49. 2010 and older

  50. Grzyb, J., Xu, F., Weiner, L., Reijerse, E.J., Lubitz, W., Nanda, V., Noy, D. De Novo Design of a Non-Natural Fold for an Iron-Sulfur Cluster Binding Site in its Central Core. BBA BioEnergetics. 2010; 1797: 406-413.

  51. Xu, F., Zhang, L., Koder, R.L., Nanda, V. De Novo Self-Assembling Collagen Heterotrimers Using Explicit Positive and Negative Design.  Biochemistry. 2010; 49: 2307-16.
    http://dx.doi.org/10.1021/bi902077d

  52. Nanda, V., Koder, R.L. Designing Artificial Enzymes By Intuition and Computation. Nature Chemistry. 2010; 2: 15-24.

  53. Annavarapu, S., Nanda, V. Mirrors in the PDB: left-handed alpha-turns guide design with D-amino acids. BMC Structural Biology. 2009; 9:61.

  54. Kar, K., Ibrar, S., Nanda, V., Getz, T., Kunapuli, S., Brodsky, B.  Aromatic Interactions Promote Self-Association of Collagen Triple-Helical Peptides to Higher Order Structures. Biochemistry. 2009; 48: 7959-68.

  55. Schmiedekamp, A.M., Nanda, V. Metal-Activated Histidine Carbon-Donor Hydrogen Bonds Contribute to Metalloprotein Folding and Function. J. Inorg. Biochem. 2009; 103: 1054-1060.

  56. Nanda, V., Xu, F., Hsieh, D. Chapter 16: Modulation of Intrinsic Protein Properties by Computational DesignIn: Protein Engineering and Design (J. Cochran and S. Park, eds.) 2009; CRC Press.

  57. McAllister, K.A., Zou, H., Cochran, F.V., Bender, G.M., Senes, A., Fry, H.C., Nanda, V., Keenan, P.A., Lear, J.D., Saven, J.G., Therien, M.J., Blasie, J.K., DeGrado, W.F. Using alpha-helical Coiled-Coils to Design Nanostructured Metalloporphyrin Arrays. J. Am. Chem. Soc. 2008; 130: 11921-11927. 

  58. Stouffer, A.L., Acharya, R., Salom, D., Levine, A.S., Di Costanzo, L., Soto, C., Tereshko, V., Nanda, V., Stayrook, S., DeGrado, W.F. Structural Basis for the Function and Inhibition of an Influenza Virus Protein Channel. Nature. 2008; 451: 596-599.

  59. Nanda, V., Schmiedekamp, A.M. Are Aromatic Carbon Donor Hydrogen Bonds Linear in Proteins? Proteins: SFB. 2008; 70: 489-497.

  60. Nanda, V. Do-it-yourself Enzymes. Nature Chemical Biology. 2008; 4:  273-275.

  61. Nanda, V., Andrianarijaona, A., Narayanan, C. The Role of Protein Homochirality in Shaping the Energy Landscape of Folding. Prot. Sci. 2007; 16: 1667-1675.
    http://dx.doi.org/10.1110/ps.072867007

  62. Senes, A., Chadi, D.C., Law, P.B., Walters, R.F.S., Nanda, V., DeGrado, W.F. Ez, a Depth-dependent Potential for Assessing the Energies of Amino Acid Side-chains into Membranes: Derivation and Applications to Determining the Orientation of Transmembrane and Interfacial Helices. J. Mol. Biol. 2007; 366: 436-448

  63. Nanda, V., DeGrado, W.F. Computational Design of Heterochiral Peptides Against a Helical Target. J. Am. Chem. Soc. 2006; 128: 809-16.
    http://dx.doi.org/10.1021/ja054452t

  64. Tatko, C., Nanda, V., Lear, J.D., DeGrado, W.F. Polar Networks Control Membrane Protein Oligomerization. J. Am. Chem. Soc. 2006; 128: 4170-4171

  65. Nanda, V., Rosenblatt, M.M., Osyczka, A., Kono, H., Getahun, Z., Dutton, P.L., Saven, J.G., DeGrado, W.F. De Novo Design of a Redox-Active Minimal Rubredoxin Mimic. J. Am. Chem. Soc. 2005; 127: 5804-5.
    http://dx.doi.org/10.1021/ja050553f

  66. Adamian, L., Nanda, V., DeGrado, W.F., Liang, J. Empirical Lipid Propensities of Amino Acid Residues in Multispan Helical Membrane Proteins. Proteins: SFB. 2005; 59: 496-509.

  67. Stouffer, A., Nanda, V., Lear, J.D., DeGrado, W.F. Sequence Determinants of a Membrane Proton Channel: An Inverse Relationship Between Stability and Function. J. Mol. Biol. 2005; 347: 169-79.

  68. Duong-Ly, K., Nanda, V., DeGrado, W.F., Howard, K.P. M2TM Tetramer Conformation Depends on Lipid Bilayer Environment. Prot. Sci. 2005; 14: 856-61.

  69. Cristian, L., Nanda, V., Lear, J.D., DeGrado, W.F. Synergistic Interactions between Aqueous and Membrane Domains of a Designed Protein Determine its Fold and Stability. J. Mol. Biol. 2005; 348: 1225-33.

  70. Cochran, F.V., Wu, S., Wang, W., Nanda, V., Saven, J.G., Therien, M.J., DeGrado, W.F. Computational De Novo Design and Characterization of a Four-Helix Bundle Protein That Selectively Binds a Non-Biological Cofactor. J. Am. Chem. Soc. 2005; 127: 1346-7.

  71. Howard, K., Liu, W., Crocker, E., Nanda, V., Lear, J., DeGrado, W.F., Smith, S.O. Rotational Orientation of Monomers Within a Designed Homo-Oligomer Transmembrane Helical Bundle. Prot. Sci. 2005; 14: 1019-24.

  72. Li, W., Metcalf, D., Gorelik, R., Li, R., Mitra, N., Nanda, V., Law, P.B., Lear, J.D., DeGrado, W.F., Bennett, J.S. A Push-Pull Mechanism for Integrin Function. Proc. Natl. Acad. Sci. 2005; 102: 1424-29.

  73. Nanda, V., DeGrado, W.F. Automated Use of Mutagenesis Data in Structure Prediction. Proteins: SFB. 2005; 59: 454-66.

  74. Khajehpour, M., Troxler, T., Nanda, V., Vanderkooi, J.M. Mellitin as a Model System for Probing Interactions Between Proteins and Cyclodextrins. Proteins: SFB. 2004; 55: 275-87.

  75. Tucker, M.J., Getahun, Z., Nanda, V., DeGrado, W.F., Gai, F. A New Method for Determining the Local Environment and Orientation of Individual Sidechains of Membrane-Binding Peptides. J. Am. Chem. Soc. 2004; 126: 5078-9.

  76. Li, R., Gorelik, R., Nanda, V., Law, P.B., Lear, J.D., DeGrado, W.F., Bennett, J.S. Dimerization of the Transmembrane Domain of Integrin alpha-IIb Subunit in Cell Membranes. J. Biol. Chem. 2004; 279(25): 26666-73.

  77. Lear, J.D., Stouffer, A.L., Gratkowski, H., Nanda, V., DeGrado, W.F. Association of a Model Transmembrane Peptide Containing Gly in a Heptad Sequence Motif. Biophys. J. 2004; 87: 3421-29.

  78. Nanda, V., DeGrado, W.F. Simulated Evolution of Emergent Chiral Structures in Polyalanine. J. Am. Chem. Soc. 2004; 126: 14459-67.

  79. Nanda, V., Brand, L. Aromatic Interactions in Homeodomains Contribute to the Low Quantum Yield of a Conserved, Buried Tryptophan. Proteins: SFG. 2000; 40: 112-25.

  80. Nanda, V., Liang, S-M., Brand, L. Hydrophobic Clustering in Acid-Denatured IL-2 and Fluorescence of a Trp NHpi H-bond. Biochem. Biophys. Res. Comm. 2000; 279: 770-8.

  81. Packard, B.Z., Komoriya, A., Nanda, V., Brand, L. Intramolecular Excitonic Dimers in Protease Substrates: Modifications of the Backbone Moiety to Probe the H-Dimer Structure. J. Phys. Chem. B. 1998; 102: 1820-7



Postdoctoral Researchers
    Hagai Raanan
Graduate Students
Jose James
Daniel Grisham

Research Scientists
Douglas Pike





National Institutes of Health – R01 GM-089949-01A
A Computational Approach to Developing Heterochiral Peptide Therapeutics 

Gordon and Betty Moore Foundation - Design of Life's Transistors




Safety

MSDS for most reagents can be found here.  Additional information is available in Room 112 in the red MSDS and SOP folder.


Contact

email:  viknanda AT gmail DOT com

phone:  732 235 5328

mail:  Vikas Nanda; CABM Room 101D; 679 Hoes Lane West; Piscataway, NJ 08854