FLOYD ROMESBERG

Summary

Affiliation: The Scripps Research Institute
Country: USA

Publications

  1. pmc Inhibition of mutation and combating the evolution of antibiotic resistance
    Ryan T Cirz
    Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA
    PLoS Biol 3:e176. 2005
  2. ncbi request reprint Multidisciplinary experimental approaches to characterizing biomolecular dynamics
    Floyd E Romesberg
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, Maildrop CVN22, La Jolla, CA 92037, USA
    Chembiochem 4:563-71. 2003
  3. ncbi request reprint A high-resolution probe of protein folding
    Laura B Sagle
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA
    J Am Chem Soc 126:3384-5. 2004
  4. pmc Minor groove hydrogen bonds and the replication of unnatural base pairs
    Shigeo Matsuda
    Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 129:5551-7. 2007
  5. ncbi request reprint Polymerase recognition and stability of fluoro-substituted pyridone nucleobase analogues
    Gil Tae Hwang
    Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Chembiochem 8:1606-11. 2007
  6. pmc Characterization of alkaline transitions in ferricytochrome c using carbon-deuterium infrared probes
    Patrick Weinkam
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 47:13470-80. 2008
  7. ncbi request reprint Efforts toward developing direct probes of protein dynamics
    Matthew E Cremeens
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 128:6028-9. 2006
  8. doi request reprint Direct observation of ligand dynamics in cytochrome c
    Megan C Thielges
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 131:6054-5. 2009
  9. pmc Molecular description of flexibility in an antibody combining site
    Jörg Zimmermann
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Phys Chem B 114:7359-70. 2010
  10. pmc Protein dynamics and the immunological evolution of molecular recognition
    Ralph Jimenez
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, Maildrop CVN22, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:3803-8. 2004

Research Grants

Collaborators

Detail Information

Publications54

  1. pmc Inhibition of mutation and combating the evolution of antibiotic resistance
    Ryan T Cirz
    Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA
    PLoS Biol 3:e176. 2005
    ..Our findings indicate that the inhibition of mutation could serve as a novel therapeutic strategy to combat the evolution of antibiotic resistance...
  2. ncbi request reprint Multidisciplinary experimental approaches to characterizing biomolecular dynamics
    Floyd E Romesberg
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, Maildrop CVN22, La Jolla, CA 92037, USA
    Chembiochem 4:563-71. 2003
  3. ncbi request reprint A high-resolution probe of protein folding
    Laura B Sagle
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA
    J Am Chem Soc 126:3384-5. 2004
    ....
  4. pmc Minor groove hydrogen bonds and the replication of unnatural base pairs
    Shigeo Matsuda
    Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 129:5551-7. 2007
    ..Thus, ortho methoxy groups should be generally useful for the effort to expand the genetic alphabet...
  5. ncbi request reprint Polymerase recognition and stability of fluoro-substituted pyridone nucleobase analogues
    Gil Tae Hwang
    Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Chembiochem 8:1606-11. 2007
    ....
  6. pmc Characterization of alkaline transitions in ferricytochrome c using carbon-deuterium infrared probes
    Patrick Weinkam
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 47:13470-80. 2008
    ..7. Native topology-based models with enforced misligation are employed to help understand the structures of the observed intermediates...
  7. ncbi request reprint Efforts toward developing direct probes of protein dynamics
    Matthew E Cremeens
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 128:6028-9. 2006
    ....
  8. doi request reprint Direct observation of ligand dynamics in cytochrome c
    Megan C Thielges
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 131:6054-5. 2009
    ..The data suggest that the associated time constant should not be used as a measure of interchain diffusion, and the results emphasize the importance of studying protein folding with probes that have inherently high structural resolution...
  9. pmc Molecular description of flexibility in an antibody combining site
    Jörg Zimmermann
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Phys Chem B 114:7359-70. 2010
    ..The results suggest that 3PEPS spectroscopy in combination with molecular dynamics simulations can provide a detailed description of protein dynamics and, in this case, how it is evolved for biological function...
  10. pmc Protein dynamics and the immunological evolution of molecular recognition
    Ralph Jimenez
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, Maildrop CVN22, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:3803-8. 2004
    ..The results also reflect the type of protein rigidification that may be important for other biological interactions, such as protein-protein, protein-ligand or protein-drug, and enzyme-substrate recognition...
  11. ncbi request reprint The effect of minor-groove hydrogen-bond acceptors and donors on the stability and replication of four unnatural base pairs
    Shigeo Matsuda
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 125:6134-9. 2003
    ....
  12. doi request reprint Direct observation of structural heterogeneity in a beta-sheet
    Matthew E Cremeens
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 131:5726-7. 2009
    ..The C-D-based IR technique should be generally useful in the characterization of structure and heterogeneity of both folded and unfolded states...
  13. pmc Chemical frustration in the protein folding landscape: grand canonical ensemble simulations of cytochrome c
    Patrick Weinkam
    Center for Theoretical Biological Physics and Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Biochemistry 48:2394-402. 2009
    ..The results demonstrate the importance of chemical frustration for understanding biomolecular energy landscapes...
  14. ncbi request reprint Optimization of interstrand hydrophobic packing interactions within unnatural DNA base pairs
    Shigeo Matsuda
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 126:14419-27. 2004
    ....
  15. pmc Efforts toward expansion of the genetic alphabet: structure and replication of unnatural base pairs
    Shigeo Matsuda
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 129:10466-73. 2007
    ..The results also help explain the replication properties of many previously examined unnatural base pairs and should help design unnatural base pairs that are better replicated...
  16. ncbi request reprint Redox-coupled dynamics and folding in cytochrome c
    Laura B Sagle
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 128:7909-15. 2006
    ..The data suggest that while the oxidized protein is not more flexible than the reduced protein, it is more locally unfolded. Local unfolding of cytochrome c might be one mechanism whereby the protein evolved to control electron transfer...
  17. doi request reprint The folding energy landscape and free energy excitations of cytochrome c
    Patrick Weinkam
    Center for Theoretical Biological Physics and Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Acc Chem Res 43:652-60. 2010
    ..Moreover, its added complexity provides a valuable means of probing the folding energy landscape in greater detail than is possible with simpler systems...
  18. pmc PCR with an expanded genetic alphabet
    Denis A Malyshev
    Department of Chemistry and Center for Protein and Nucleic Acid Research, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 131:14620-1. 2009
    ..Importantly, the results reveal that the unnatural base pairs may function within an expanded genetic alphabet and make possible many in vitro applications...
  19. doi request reprint Development of a universal nucleobase and modified nucleobases for expanding the genetic code
    Floyd E Romesberg
    The Scripps Research Institute, La Jolla, California, USA
    Curr Protoc Nucleic Acid Chem . 2002
    ..Determination of the thermodynamic and kinetic parameters of unnatural nucleosides is accomplished by incorporation into oligonucleotides and subsequent evaluation as described herein...
  20. pmc Major groove derivatization of an unnatural base pair
    Young Jun Seo
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Chembiochem 10:2394-400. 2009
    ....
  21. pmc The determinants of stability and folding in evolutionarily diverged cytochromes c
    Megan C Thielges
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Mol Biol 388:159-67. 2009
    ..Furthermore, we show that the differences in stability and folding appear to result from a single amino acid substitution that stabilizes a helix by allowing for increased solvation of its N-terminus...
  22. doi request reprint C-D modes of deuterated side chain of leucine as structural reporters via dual-frequency two-dimensional infrared spectroscopy
    Sri Ram G Naraharisetty
    Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA
    J Phys Chem B 113:4940-6. 2009
    ....
  23. ncbi request reprint Determinants of unnatural nucleobase stability and polymerase recognition
    Allison A Henry
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA
    J Am Chem Soc 125:9638-46. 2003
    ..The data are useful for designing stable and replicable third base pairs and for understanding the contributions of nucleobase shape, polarity, and polarizability to the stability and replication of DNA...
  24. ncbi request reprint Stability and selectivity of unnatural DNA with five-membered-ring nucleobase analogues
    Markus Berger
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 124:1222-6. 2002
    ..These results expand the potential nucleobase analogues with which the genetic alphabet may be expanded to include five-membered-ring heterocycles...
  25. ncbi request reprint Efforts to expand the genetic alphabet: identification of a replicable unnatural DNA self-pair
    Allison A Henry
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 126:6923-31. 2004
    ..The most promising unnatural base pair candidate of this series is the 3-fluorobenzene self-pair, which is replicated with reasonable efficiency and selectivity...
  26. ncbi request reprint Beyond A, C, G and T: augmenting nature's alphabet
    Allison A Henry
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, Maildrop CVN22, La Jolla, CA 92037, USA
    Curr Opin Chem Biol 7:727-33. 2003
    ..This review provides a critical comparison of the third base pair candidates and discusses the further work required to expand the genetic alphabet...
  27. pmc Synthesis and biological evaluation of 2',4'- and 3',4'-bridged nucleoside analogues
    K C Nicolaou
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Bioorg Med Chem 19:5648-69. 2011
    ..0 μM) and HxB2 (IC(50)=2.4 μM). These findings render bridged nucleosides as credible leads for drug discovery in the anti-HIV area of research...
  28. pmc Optimization of an unnatural base pair toward natural-like replication
    Young Jun Seo
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 131:3246-52. 2009
    ....
  29. pmc Unnatural substrate repertoire of A, B, and X family DNA polymerases
    Gil Tae Hwang
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 130:14872-82. 2008
    ..T7-mediated replication is especially noteworthy due to strong mispair discrimination...
  30. doi request reprint Exploring the energy landscape of antibody-antigen complexes: protein dynamics, flexibility, and molecular recognition
    Megan C Thielges
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Biochemistry 47:7237-47. 2008
    ..The data also provide a gauge of the dynamic diversity of the antibody repertoire and suggest that this diversity might contribute to molecular recognition by facilitating the recognition of the broadest range of foreign molecules...
  31. ncbi request reprint Direct and high resolution characterization of cytochrome c equilibrium folding
    Laura B Sagle
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 128:14232-3. 2006
    ..The inherently fast time scale of IR also allows us to characterize the folding intermediate, long thought to be present, but which has proven difficult to characterize by other techniques...
  32. pmc Flexibility and molecular recognition in the immune system
    Ralph Jimenez
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Drop CVN22, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 100:92-7. 2003
    ..The binding site flexibilities may result in varying mechanisms of antigen recognition including lock-and-key, induced-fit, and conformational selection...
  33. ncbi request reprint Polymerase recognition of unnatural base pairs
    Chengzhi Yu
    Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Angew Chem Int Ed Engl 41:3841-4. 2002
  34. pmc Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics
    Jörg Zimmermann
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 103:13722-7. 2006
    ..This study demonstrates how protein dynamics may be tailored by evolution and has important implications for our understanding of how novel protein functions are evolved...
  35. pmc Type I signal peptidase and protein secretion in Staphylococcus epidermidis
    Michael E Powers
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    J Bacteriol 193:340-8. 2011
    ....
  36. pmc In vitro activities of arylomycin natural-product antibiotics against Staphylococcus epidermidis and other coagulase-negative staphylococci
    Peter A Smith
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Antimicrob Agents Chemother 55:1130-4. 2011
    ..While the susceptibility was generally correlated with the absence of the previously identified Pro residue, several cases were identified where additional factors also appear to contribute...
  37. ncbi request reprint Protein dynamics and cytochrome c: correlations between ligand vibrations and redox activity
    Jodie K Chin
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 124:1846-7. 2002
    ..Therefore, although the ligand dynamics depend on the protein's redox state, there are no detected differences in protein dynamics of the oxidized and reduced proteins...
  38. pmc Polymerase evolution: efforts toward expansion of the genetic code
    Aaron M Leconte
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 127:12470-1. 2005
    ..The evolved properties of P2, as well as the observed mutations, are consistent with an increased affinity for the DNA primer-template containing the self-pair...
  39. pmc Transcription of an expanded genetic alphabet
    Young Jun Seo
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 131:5046-7. 2009
    ..The results also demonstrate that d5SICS:dNaM is both replicated and transcribed with efficiencies and fidelities that should be sufficient for use as part of an in vitro expanded genetic alphabet...
  40. pmc Substituent effects on the pairing and polymerase recognition of simple unnatural base pairs
    Gil Tae Hwang
    Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Nucleic Acids Res 34:2037-45. 2006
    ..The results help identify the determinants of base pair stability and efficient replication and should contribute to the effort to develop stable and replicable unnatural base pairs...
  41. pmc Optimization of unnatural base pair packing for polymerase recognition
    Shigeo Matsuda
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 128:6369-75. 2006
    ..Combined with our previous results, these studies suggest that appropriately derivatized phenyl nucleobase analogues represent a promising approach toward developing a third base pair and expanding the genetic alphabet...
  42. pmc Role of Doa1 in the Saccharomyces cerevisiae DNA damage response
    Ewa T Lis
    Department of Chemistry, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell Biol 26:4122-33. 2006
    ..The data suggest that Doa1 is the major source of ubiquitin for the DNA damage response and that Doa1 also plays an additional essential and more specific role in the monoubiquitination of histone H2B...
  43. pmc An efficiently extended class of unnatural base pairs
    Aaron M Leconte
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Am Chem Soc 128:6780-1. 2006
    ..Screening, when complemented by further kinetic analysis, can improve the understanding of the determinants of efficient extension as well as identify viable hetero base pairs...
  44. pmc Pph3-Psy2 is a phosphatase complex required for Rad53 dephosphorylation and replication fork restart during recovery from DNA damage
    Bryan M O'Neill
    Departments of Chemistry and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 104:9290-5. 2007
    ..These findings suggest that Rad53 regulates replication fork restart and initiation of late firing origins independently and that regulation of these processes is mediated by specific Rad53 phosphatases...
  45. ncbi request reprint Structural and initial biological analysis of synthetic arylomycin A2
    Tucker C Roberts
    Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California, 92037, USA
    J Am Chem Soc 129:15830-8. 2007
    ..Thus, these studies help identify the determinants of the biological activity of arylomycin A2 and should aid in the design of analogs to further explore and develop this novel class of antibiotic...
  46. pmc Discovery, characterization, and optimization of an unnatural base pair for expansion of the genetic alphabet
    Aaron M Leconte
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA
    J Am Chem Soc 130:2336-43. 2008
    ..From the results of these studies, we designed an optimized base pair, d5SICS:dMMO2, which is efficiently and selectively synthesized by Kf within the context of natural DNA...
  47. pmc Carbon-deuterium bonds as probes of dihydrofolate reductase
    Megan C Thielges
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA
    J Am Chem Soc 130:6597-603. 2008
    ....
  48. ncbi request reprint Efforts towards expansion of the genetic alphabet: pyridone and methyl pyridone nucleobases
    Aaron M Leconte
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Angew Chem Int Ed Engl 45:4326-9. 2006
  49. ncbi request reprint Stability and polymerase recognition of pyridine nucleobase analogues: role of minor-groove H-bond acceptors
    Yoonkyung Kim
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Angew Chem Int Ed Engl 45:7809-12. 2006
  50. ncbi request reprint Differential solvation and tautomer stability of a model base pair within the minor and major grooves of DNA
    Francois Yves Dupradeau
    Faculté de Pharmacie and DMAG EA 3901, Universite de Picardie Jules Verne, Amiens, France
    J Am Chem Soc 127:15612-7. 2005
    ..The differential stabilization of the enol and keto tautomers in the major and minor grooves may reflect the functions for which these environments evolved, including duplex replication, stability, and recognition...
  51. ncbi request reprint Chemical biology: a broader take on DNA
    Aaron M Leconte
    Nature 444:553-5. 2006
  52. ncbi request reprint Side effects may include evolution
    Ryan T Cirz
    Nat Med 12:890-1. 2006
  53. ncbi request reprint Amplify this! DNA and RNA get a third base pair
    Aaron M Leconte
    Nat Methods 3:667-8. 2006
  54. ncbi request reprint Infrared line shape of an alpha-carbon deuterium-labeled amino acid
    Carrie S Kinnaman
    Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
    J Am Chem Soc 128:13334-5. 2006
    ....

Research Grants15

  1. Expanding the Genetic Alphabet by Design and Selection
    FLOYD ROMESBERG; Fiscal Year: 2009
    ..Figure 1. The d5SICS:dNaM base pair ..
  2. Evolving Novel Polymerases for Genome Sequencing
    FLOYD ROMESBERG; Fiscal Year: 2007
    ....
  3. Expanding the Genetic Alphabet by Design and Selection
    FLOYD ROMESBERG; Fiscal Year: 2007
    ..Finally, we will begin to explore the transcription of the self-pair into unnatural RNA, the next step toward expanding an organism's genetic code, laying the foundation for a semi-synthetic organism. ..
  4. Pathways Controlling Genome Stability and Mutation
    FLOYD ROMESBERG; Fiscal Year: 2007
    ..These studies are expected to help understand when and how eukaryotic cells mutate, and will contribute to our understanding of issues that are of fundamental significance to human health, such as aging and cancer. ..
  5. EXPANDING THE GENETIC ALPHABET BY POLYMERASE EVOLUTION
    FLOYD ROMESBERG; Fiscal Year: 2003
    ..A third base pair would also allow for the creation of additional codons, which would facilitate the incorporation of unnatural amino acids into proteins. ..
  6. Expanding the Genetic Alphabet by Design and Selection
    Floyd E Romesberg; Fiscal Year: 2010
    ..Figure 1. The d5SICS:dNaM base pair ..