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Paul D. Boyer Professor of Molecular Biology & Biochemistry,
Molecular Biology Institute
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Distinguished Professor,
Biological Chemistry | |
Professor,
Chemistry and Biochemistry | |
Director,
UCLA-DOE Institute for Genomics & Proteomics | |
Lab Director,
Eisenberg Lab
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Education: |
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Degrees:
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Ph.D., Oxford University, 1964
M.A., Cambridge, 1961
A.B., Harvard College
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Honors and Awards: |
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UCLA, McCoy Award
Amgen Award of the Protein Society
Pierce Award of the Immunotoxin Society
2008 Biophysical Society, Emily M. Gray Award
2008 Preceptor for the 2009 Nobel Laureate Signature Award for Graduate Education in Chemistry
2008 Technion - Israel Institute of Technology, Harvey Prize in Human Health
2005 Harvard, Westheimer Medal
2004 UCLA, Seaborg Medal
2001 Howard Hughes Medical Institute, Investigator
1989 National Academy of Sciences, Elected Member
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Professional Societies: |
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American Association for the Advancement of Science, Fellow
American Philosophical Society, Member
Institute of Medicine, Member
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Contact Information:
| Laboratory Address: |
Paul Boyer Hall 205
UNITED STATES
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| Mailing Address: |
201A Paul Boyer Hall
CAMPUS - 157005
Los Angeles, CA
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| Work Address: |
Paul Boyer Hall 201A
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Fax Number:
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(310) 206-3914
fax
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Work Phone Number:
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1 (310) 825-3754
Office
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Lab Number:
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1 (310) 206-3642
Lab
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Research Interests:
Protein Structure, folding and design In our group, protein structures are determined by x-ray crystallography, and structures are related to function by biochemical and genetic methods. At present the structure and action of half a dozen proteins are being studied. These include the multisubunit, regulated enzymes glutamine synthetase and RuBisCO; diphtheria toxin, a proenzyme that crosses the cell plasma membrane and stops protein synthesis; and several designed proteins. Excellent facilities for structure determination and computation are shared with other members of the Biological Structure Group. A central question of biochemistry is how the amino acids sequence of a protein determines its three dimensional structure. The goal is to be able to predict the structure from the sequence, a matter of great practical importance. One computational approach is being developed to describe a 3D structure by a 3D profile. The 3D profile can score the compatibility of any amino acid sequence with the 3D structure. A high compatibility score indicates the sequence may be folded as the structure. A second approach is to test rules of protein folding by designing and synthesizing a simple protein, and then using x-ray crystallography to compare the actual structure with the design. What are the interactions that stabilize proteins or which permits proteins to recognize other proteins or small molecules? These questions are being explored with hydrophobic moments and Atomic Solvation Parameters (ASPs). These are semi-empirical quantities that characterize interactions of amino acid residues. ASPs give an estimate of the hydrophobic contribution to the free energy of interaction.
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Technical Research Interest:
Our long term goal is to understand and manipulate the metabolism
of cells through the interactions of their constituent
proteins. One goal is to be able to infer functional linkages
of proteins, on the basis of genome sequences and protein
expression data. Computational methods have been developed
for establishing these relationships, including the phylogenetic
profile and Rosetta Stone methods. To benchmark these computational
methods, a large Database of Interacting Proteins has
been built up. X-ray crystallography remains a powerful tool for
exploring protein structure and interactions. Our X-ray projects
are of two types. The first are on amyloids and prions, pathologically
interacting proteins. The goal is to understand the
structures that underlie the pathologies. The other projects are
on the structural biology of Mycobacterium tuberculosis, as
part of the TB Structural Genomics Consortium.
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Additional Information:
David Eisenberg is currently Professor of Chemistry and Biochemistry and Biological Chemistry, as well as HHMI Investigator and Director of the UCLA-DOE Institute for Genomics and Proteomics. Before he came to UCLA, Eisenberg earned an A.B. in Biochemical Sciences from Harvard College and a D.Phil. from Oxford University in Theoretical Chemistry on a Rhodes Scholarship. After postdoctoral study at Princeton University on water and hydrogen bonding and at Caltech on protein crystallography, he joined the faculty at UCLA. Currently he studies protein interactions by X-ray crystallography, bioinformatics, and biochemistry, with an emphasis on amyloid-forming proteins. This recently recognized protein state offers opportunities to understand cells in health and disease, and in synthesizing new materials and in understanding processes as diverse as biofilms and corrosion. Eisenberg has published over 300 papers and reviews, holds half a dozen patents. His awards include: the UCLA Distinguished Teaching Award, John Simon Guggenheim Fellowship, the UCLA Faculty Research Lectureship, the Stein and Moore Award of the Protein Society, the ACS Faculty Mentoring Award, and membership in the National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society, and the Institute of Medicine.
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Cong Liu, Michael R Sawaya & David Eisenberg, ?2-microglobulin forms three-dimensional domain-swapped amyloid fibrils with disulfide linkages, Nature Structural & Molecular Biology, 2011, 18, 49-55.
Apostol MI, Sawaya MR, Cascio D, Eisenberg D, Crystallographic studies of prion protein (PrP) segments suggest how structural changes encoded by polymorphism at residue 129 modulate susceptibility to human prion disease, J Biol Chem. , 2010, 285 (39), 29671-5.
Wang Lei, Schubert David, Sawaya Michael R, Eisenberg David, Riek Roland, Multidimensional Structure-Activity Relationship of a Protein in Its Aggregated States., Angewandte Chemie, 2010, 49 (23), 3904-8.
Eisenberg David L, Stika Catherine, Desai Ami, Baker David, Yost Kathleen J, Providing contraception for women taking potentially teratogenic
medications: a survey of internal medicine physicians' knowledge,
attitudes and barriers., Journal of general internal medicine, 2010, 25 (4), 291-7.
Khakshoor O, Lin AJ, Korman TP, Sawaya MR, Tsai SC, Eisenberg D, Nowick JS, X-ray crystallographic structure of an artificial beta-sheet dimer, J Am Chem Soc., 2010, 132 (33), 11622-8.
Wiltzius JJ, Sievers SA, Sawaya MR, Eisenberg D, Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process, Protein Science, 2009, 18 (7), 1521-30.
Sprinzak Einat, Cokus Shawn J, Yeates Todd O, Eisenberg David, Pellegrini Matteo, Detecting coordinated regulation of multi-protein complexes using
logic analysis of gene expression., BMC systems biology, 2009, 3 (1), 115.
Maji Samir K, Perrin Marilyn H, Sawaya Michael R, Jessberger Sebastian, Vadodaria Krishna, Rissman Robert A, Singru Praful S, Nilsson K Peter R, Simon Rozalyn, Schubert David, Eisenberg David, Rivier Jean, Sawchenko Paul, Vale Wylie, Riek Roland, Functional amyloids as natural storage of peptide hormones in
pituitary secretory granules., Science (New York, N.Y.), 2009, 325 (5938), 328-32.
Wiltzius Jed J W, Landau Meytal, Nelson Rebecca, Sawaya Michael R, Apostol Marcin I, Goldschmidt Lukasz, Soriaga Angela B, Cascio Duilio, Rajashankar Kanagalaghatta, Eisenberg David, Molecular mechanisms for protein-encoded inheritance., Nature structural & molecular biology, 2009, 16 (9), 973-8.
Salwinski Lukasz, Licata Luana, Winter Andrew, Thorneycroft David, Khadake Jyoti, Ceol Arnaud, Aryamontri Andrew Chatr, Oughtred Rose, Livstone Michael, Boucher Lorrie, Botstein David, Dolinski Kara, Berardini Tanya, Huala Eva, Tyers Mike, Eisenberg David, Cesareni Gianni, Hermjakob Henning, Recurated protein interaction datasets., Nature methods, 2009, 6 (12), 860-1.
Miallau Linda, Faller Michael, Chiang Janet, Arbing Mark, Guo Feng, Cascio Duilio, Eisenberg David, Structure and proposed activity of a member of the VapBC family of
toxin-antitoxin systems. VapBC-5 from Mycobacterium tuberculosis., The Journal of biological chemistry, 2009, 284 (1), 276-83.
Sawaya, M. R. Wojtowicz, W. M. Andre, I. Qian, B. Wu, W. Baker, D. Eisenberg, D. Zipursky, S. L. , A double S shape provides the structural basis for the extraordinary binding specificity of Dscam isoforms, Cell, 2008, 134 ( 6), 1007-18.
Wiltzius JJ, Sievers SA, Sawaya MR, Cascio D, Popov D, Riekel C, Eisenberg D, Atomic Structure of the Cross-Beta Spine of Islet Amyloid Polypeptide, Protein Science, 2008, 17 (9), 1467-74.
Wang L, Maji SK, Sawaya MR, Eisenberg D, Riek R, Bacterial Inclusion Bodies Contain Amyloid-Like Structure, PLoS Biol, 2008, 6 (8).
Cruz, Watson, Miller, Montoya, Ochoa, Sieling, Gutierrez, Navab, Reddy, Witztum, Fogelman, Rea, Eisenberg, Berliner, Modlin, Host-derived oxidized phospholipids and HDL regulate innate immunity in human leprosy., J. Clin. Invest., 2008.
Riley, R., Pellegrini, M., Eisenberg, D., Identifying Cognate Binding Pairs Among a Large set of Paralogs: the Case of PE/PPE Proteins of Mycobacterium Tuberculosis, PLoS Comput. Biol., 2008, 4 (9).
Medrano-Soto, A. Pal, D. Eisenberg, D. , Inferring molecular function: contributions from functional linkages, Trends Genet, 2008, 24 ( 12), 587-90.
Dunn B., Long J.W., Rolison D.R., Rethinking Multifunctions in Three Dimensions for Miniaturizing Electrical Energy Storage, Interface, 2008, 17 (3), 49.
Guo, Z. Eisenberg, D. , The structure of a fibril-forming sequence, NNQQNY, in the context of a globular fold, Protein Sci, 2008, 17 ( 9), 1617-23.
Miller Christopher S, Eisenberg David, Using inferred residue contacts to distinguish between correct and incorrect protein models., Bioinformatics, 2008, 24 (14), 1575-82.
White, E. L. Southworth, K. Ross, L. Cooley, S. Gill, R. B. Sosa, M. I. Manouvakhova, A. Rasmussen, L. Goulding, C. Eisenberg, D. Fletcher, T. M., 3rd , A novel inhibitor of Mycobacterium tuberculosis pantothenate synthetase, J Biomol Screen, 2007, 12 ( 1), 100-5.
Sawaya Michael R, Sambashivan Shilpa, Nelson Rebecca, Ivanova Magdalena I, Sievers Stuart A, Apostol Marcin I, Thompson Michael J, Balbirnie Melinda, Wiltzius Jed J W, McFarlane Heather T, Madsen Anders Ã, Riekel Christian, Eisenberg David, Atomic structures of amyloid cross-beta spines reveal varied steric zippers., Nature, 2007, 447 (7143), 453-7.
Galynker,, II Eisenberg, D. Matochik, J. A. Gertmenian-King, E. Cohen, L. Kimes, A. S. Contoreggi, C. Kurian, V. Ernst, M. Rosenthal, R. N. Prosser, J. London, E. D. , Cerebral metabolism and mood in remitted opiate dependence, Drug Alcohol Depend, 2007, 90 ( 2-3), 166-74.
Tsemekhman, K. Goldschmidt, L. Eisenberg, D. Baker, D. , Cooperative hydrogen bonding in amyloid formation, Protein Sci, 2007, 16 ( 4), 761-4.
Anderson Daniel H, Kickhoefer Valerie A, Sievers Stuart A, Rome Leonard H, Eisenberg David, Draft crystal structure of the vault shell at 9-A resolution., PLoS Biol., 2007, 5 (11), e318.
Kim Sul-Min, Bowers Peter M, Pal Debnath, Strong Michael, Terwilliger Thomas C, Kaufmann Markus, Eisenberg David, Functional linkages can reveal protein complexes for structure determination., Structure, 2007, 15 (9), 1079-89.
Salwinski Lukasz, Eisenberg David, The MiSink Plugin: Cytoscape as a graphical interface to the Database of Interacting Proteins., Bioinformatics, 2007, 23 (16), 2193-5.
Guo Zhefeng, Eisenberg David, The mechanism of the amyloidogenic conversion of T7 endonuclease I., J. Biol. Chem., 2007, 282 (20), 14968-74.
Sandra Orchard, Lukasz Salwinski, Samuel Kerrien, Luisa Montecchi-Palazzi, Matthias Oesterheld, Volker Stümpflen, Arnaud Ceol, Andrew Chatr-aryamontri, John Armstrong, Peter Woollard, John J Salama, Susan Moore, Jérôme Wojcik, Gary D Bader, Marc Vidal, Michael E Cusick, Mark Gerstein, Anne-Claude Gavin, Giulio Superti-Furga, Jack Greenblatt, Joel Bader, Peter Uetz, Mike Tyers, Pierre Legrain, Stan Fields, Nicola Mulder, Michael Gilson, Michael Niepmann, Lyle Burgoon, Javier De Las Rivas, Carlos Prieto, Victoria M Perreau, Chris Hogue, Hans-Werner Mewes, Rolf Apweiler, Ioannis Xenarios, David Eisenberg, Gianni Cesareni & Henning Hermjakob, The minimum information required for reporting a molecular interaction experiment (MIMIx), Nature Biotechnology, 2007, 25, 894-8.
Kuriyan John, Eisenberg David, The origin of protein interactions and allostery in colocalization., Nature, 2007, 450 (7172), 983-90.
Strong Michael, Eisenberg David, The protein network as a tool for finding novel drug targets., Mol. Ther., 2007, 64 (1), 191, 193-215.
Goulding Celia W, Bowers Peter M, Segelke Brent, Lekin Tim, Kim Chang-Yub, Terwilliger Thomas C, Eisenberg David, The structure and computational analysis of Mycobacterium tuberculosis protein CitE suggest a novel enzymatic function., J. Mol. Biol., 2007, 365 (2), 275-83.
Goldschmidt Lukasz, Cooper David R, Derewenda Zygmunt S, Eisenberg David, Toward rational protein crystallization: A Web server for the design of crystallizable protein variants., Protein Sci., 2007, 16 (8), 1569-76.
Ivanova, M. I. Thompson, M. J. Eisenberg, D. , A systematic screen of beta(2)-microglobulin and insulin for amyloid-like segments, Proc Natl Acad Sci U S A, 2006, 103 ( 11), 4079-82.
Eisenberg, D. Marcotte, E. McLachlan, A. D. Pellegrini, M. , Bioinformatic challenges for the next decade(s), Philos Trans R Soc Lond B Biol Sci, 2006, 361 ( 1467), 525-7.
Bennett Melanie J, Sawaya Michael R, Eisenberg David, Deposition diseases and 3D domain swapping., Structure, 2006, 14 (5), 811-24.
Nelson, R. Eisenberg, D. , Recent atomic models of amyloid fibril structure, Curr Opin Struct Biol, 2006, 16 ( 2), 260-5.
Guo Zhefeng, Eisenberg David, Runaway domain swapping in amyloid-like fibrils of T7 endonuclease I., Proc. Natl. Acad. Sci. U.S.A., 2006, 103 (21), 8042-7.
Nelson Rebecca, Eisenberg David, Structural models of amyloid-like fibrils., Adv. Protein Chem., 2006, 73 (2), 235-82.
Thompson, M. J. Sievers, S. A. Karanicolas, J. Ivanova, M. I. Baker, D. Eisenberg, D. , The 3D profile method for identifying fibril-forming segments of proteins, Proc Natl Acad Sci U S A, 2006, 103 ( 11), 4074-8.
Eisenberg, D. Nelson, R. Sawaya, M. R. Balbirnie, M. Sambashivan, S. Ivanova, M. I. Madsen, A. O. Riekel, C. , The structural biology of protein aggregation diseases: Fundamental questions and some answers, Acc Chem Res, 2006, 39 ( 9), 568-75.
Strong Michael, Sawaya Michael R, Wang Shuishu, Phillips Martin, Cascio Duilio, Eisenberg David, Toward the structural genomics of complexes: crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis., Proc. Natl. Acad. Sci. U.S.A., 2006, 103 (21), 8060-5.
Sambashivan, S. Liu, Y. Sawaya, M. R. Gingery, M. Eisenberg, D. , Amyloid-like fibrils of ribonuclease A with three-dimensional domain-swapped and native-like structure, Nature, 2005, 437 ( 7056), 266-9.
Li, H. Pellegrini, M. Eisenberg, D. , Detection of parallel functional modules by comparative analysis of genome sequences, Nat Biotechnol, 2005, 23 ( 2), 253-60.
Nelson, R. Sawaya, M. R. Balbirnie, M. Madsen, A. O. Riekel, C. Grothe, R. Eisenberg, D. , Structure of the cross-beta spine of amyloid-like fibrils, Nature, 2005, 435 ( 7043), 773-8.
Bowers, P. M. O'Connor, B. D. Cokus, S. J. Sprinzak, E. Yeates, T. O. Eisenberg, D. , Utilizing logical relationships in genomic data to decipher cellular processes, FEBS J, 2005, 272 ( 20), 5110-8.
Ivanova, M. I. Sawaya, M. R. Gingery, M. Attinger, A. Eisenberg, D. , An amyloid-forming segment of beta2-microglobulin suggests a molecular model for the fibril, Proc Natl Acad Sci U S A, 2004, 101 ( 29), 10584-9.
Goulding, C. W. Apostol, M. I. Gleiter, S. Parseghian, A. Bardwell, J. Gennaro, M. Eisenberg, D. , Gram-positive DsbE proteins function differently from Gram-negative DsbE homologs. A structure to function analysis of DsbE from Mycobacterium tuberculosis, J Biol Chem, 2004, 279 ( 5), 3516-24.
Kleiger, G. Panina, E. M. Mallick, P. Eisenberg, D. , PFIT and PFRIT: bioinformatic algorithms for detecting glycosidase function from structure and sequence, Protein Sci, 2004, 13 ( 1), 221-9.
Salwinski, L. Miller, C. S. Smith, A. J. Pettit, F. K. Bowie, J. U. Eisenberg, D. , The Database of Interacting Proteins: 2004 update, Nucleic Acids Res, 2004, 32 ( Database issue), D449-51.
Bowers, P. M. Cokus, S. J. Eisenberg, D. Yeates, T. O. , Use of logic relationships to decipher protein network organization, Science, 2004, 306 ( 5705), 2246-9.
Salwinski, L. Eisenberg, D. , Computational methods of analysis of protein-protein interactions, Curr Opin Struct Biol, 2003, 13 ( 3), 377-82.
Wang, S. Eisenberg, D. , Crystal structures of a pantothenate synthetase from M. tuberculosis and its complexes with substrates and a reaction intermediate, Protein Sci, 2003, 12 ( 5), 1097-108.
Anderson, D. H. Sawaya, M. R. Cascio, D. Ernst, W. Modlin, R. Krensky, A. Eisenberg, D. , Granulysin crystal structure and a structure-derived lytic mechanism, J Mol Biol, 2003, 325 ( 2), 355-65.
Strong, M. Mallick, P. Pellegrini, M. Thompson, M. J. Eisenberg, D. , Inference of protein function and protein linkages in Mycobacterium tuberculosis based on prokaryotic genome organization: a combined computational approach, Genome Biol, 2003, 4 ( 9), R59.
Ivanova, M. I. Gingery, M. Whitson, L. J. Eisenberg, D. , Role of the C-terminal 28 residues of beta2-microglobulin in amyloid fibril formation, Biochemistry, 2003, 42 ( 46), 13536-40.
Lee, S. Eisenberg, D. , Seeded conversion of recombinant prion protein to a disulfide-bonded oligomer by a reduction-oxidation process, Nat Struct Biol, 2003, 10 ( 9), 725-30.
McCarty, A. S. Kleiger, G. Eisenberg, D. Smale, S. T. , Selective dimerization of a C2H2 zinc finger subfamily, Mol Cell, 2003, 11 ( 2), 459-70.
Cech, T. R. Eddy, S. R. Eisenberg, D. Hersey, K. Holtzman, S. H. Poste, G. H. Raikhel, N. V. Scheller, R. H. Singer, D. B. Waltham, M. C. , Sharing publication-related data and materials: responsibilities of authorship in the life sciences, Plant Physiol, 2003, 132 ( 1), 19-24.
Mura, C. Phillips, M. Kozhukhovsky, A. Eisenberg, D. , Structure and assembly of an augmented Sm-like archaeal protein 14-mer, Proc Natl Acad Sci U S A, 2003, 100 ( 8), 4539-44.
Mura, C. Katz, J. E. Clarke, S. G. Eisenberg, D. , Structure and function of an archaeal homolog of survival protein E (SurEalpha): an acid phosphatase with purine nucleotide specificity, J Mol Biol, 2003, 326 ( 5), 1559-75.
Eisenberg, D. , The discovery of the alpha-helix and beta-sheet, the principal structural features of proteins, Proc Natl Acad Sci U S A, 2003, 100 ( 20), 11207-10.
Hsu, T. Hingley-Wilson, S. M. Chen, B. Chen, M. Dai, A. Z. Morin, P. M. Marks, C. B. Padiyar, J. Goulding, C. Gingery, M. Eisenberg, D. Russell, R. G. Derrick, S. C. Collins, F. M. Morris, S. L. King, C. H. Jacobs, W. R., Jr. , The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue, Proc Natl Acad Sci U S A, 2003, 100 ( 21), 12420-5.
Strong, M. Graeber, T. G. Beeby, M. Pellegrini, M. Thompson, M. J. Yeates, T. O. Eisenberg, D. , Visualization and interpretation of protein networks in Mycobacterium tuberculosis based on hierarchical clustering of genome-wide functional linkage maps, Nucleic Acids Res, 2003, 31 ( 24), 7099-109.
Liu, Y. Eisenberg, D. , 3D domain swapping: as domains continue to swap, Protein Sci, 2002, 11 ( 6), 1285-99.
Duan, X. J. Xenarios, I. Eisenberg, D. , Describing biological protein interactions in terms of protein states and state transitions: the LiveDIP database, Mol Cell Proteomics, 2002, 1 ( 2), 104-16.
Kleiger, G. Grothe, R. Mallick, P. Eisenberg, D. , GXXXG and AXXXA: common alpha-helical interaction motifs in proteins, particularly in extremophiles, Biochemistry, 2002, 41 ( 19), 5990-7.
Kleiger, G. Eisenberg, D. , GXXXG and GXXXA motifs stabilize FAD and NAD(P)-binding Rossmann folds through C(alpha)-H... O hydrogen bonds and van der waals interactions, J Mol Biol, 2002, 323 ( 1), 69-76.
Deane, C. M. Salwinski, L. Xenarios, I. Eisenberg, D. , Protein interactions: two methods for assessment of the reliability of high throughput observations, Mol Cell Proteomics, 2002, 1 ( 5), 349-56.
Liu, Y. Gotte, G. Libonati, M. Eisenberg, D. , Structures of the two 3D domain-swapped RNase A trimers, Protein Sci, 2002, 11 ( 2), 371-80.
Mallick, P. Weiss, R. Eisenberg, D. , The directional atomic solvation energy: an atom-based potential for the assignment of protein sequences to known folds, Proc Natl Acad Sci U S A, 2002, 99 ( 25), 16041-6.
Goulding, C. W. Sawaya, M. R. Parseghian, A. Lim, V. Eisenberg, D. Missiakas, D. , Thiol-disulfide exchange in an immunoglobulin-like fold: structure of the N-terminal domain of DsbD, Biochemistry, 2002, 41 ( 22), 6920-7.
Kleiger, G. Perry, J. Eisenberg, D. , 3D structure and significance of the GPhiXXG helix packing motif in tetramers of the E1beta subunit of pyruvate dehydrogenase from the archeon Pyrobaculum aerophilum, Biochemistry, 2001, 40 ( 48), 14484-92.
Graeber, T. G. Eisenberg, D. , Bioinformatic identification of potential autocrine signaling loops in cancers from gene expression profiles, Nat Genet, 2001, 29 ( 3), 295-300.
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