Research Topics
| FLOYD ROMESBERGSummaryAffiliation: The Scripps Research Institute Country: USA Publications
Research Grants
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Detail Information
Publications
Inhibition of mutation and combating the evolution of antibiotic resistanceRyan 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...
Multidisciplinary experimental approaches to characterizing biomolecular dynamicsFloyd 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- A high-resolution probe of protein foldingLaura 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.... - Minor groove hydrogen bonds and the replication of unnatural base pairsShigeo 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... - Polymerase recognition and stability of fluoro-substituted pyridone nucleobase analoguesGil Tae Hwang
Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
Chembiochem 8:1606-11. 2007.... - Characterization of alkaline transitions in ferricytochrome c using carbon-deuterium infrared probesPatrick 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... - Efforts toward developing direct probes of protein dynamicsMatthew 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.... 
Direct observation of ligand dynamics in cytochrome cMegan 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...- Molecular description of flexibility in an antibody combining siteJörg 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... - Protein dynamics and the immunological evolution of molecular recognitionRalph 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... - The effect of minor-groove hydrogen-bond acceptors and donors on the stability and replication of four unnatural base pairsShigeo 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.... - Direct observation of structural heterogeneity in a beta-sheetMatthew 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... - Chemical frustration in the protein folding landscape: grand canonical ensemble simulations of cytochrome cPatrick 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... - Optimization of interstrand hydrophobic packing interactions within unnatural DNA base pairsShigeo 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.... - Efforts toward expansion of the genetic alphabet: structure and replication of unnatural base pairsShigeo 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... - Redox-coupled dynamics and folding in cytochrome cLaura 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... - The folding energy landscape and free energy excitations of cytochrome cPatrick 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... - PCR with an expanded genetic alphabetDenis 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... - Development of a universal nucleobase and modified nucleobases for expanding the genetic codeFloyd 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... - Major groove derivatization of an unnatural base pairYoung Jun Seo
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
Chembiochem 10:2394-400. 2009.... - The determinants of stability and folding in evolutionarily diverged cytochromes cMegan 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... - C-D modes of deuterated side chain of leucine as structural reporters via dual-frequency two-dimensional infrared spectroscopySri Ram G Naraharisetty
Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, USA
J Phys Chem B 113:4940-6. 2009.... - Determinants of unnatural nucleobase stability and polymerase recognitionAllison 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... - Stability and selectivity of unnatural DNA with five-membered-ring nucleobase analoguesMarkus 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... - Efforts to expand the genetic alphabet: identification of a replicable unnatural DNA self-pairAllison 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... - Beyond A, C, G and T: augmenting nature's alphabetAllison 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... - Synthesis and biological evaluation of 2',4'- and 3',4'-bridged nucleoside analoguesK 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... - Optimization of an unnatural base pair toward natural-like replicationYoung 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.... - Unnatural substrate repertoire of A, B, and X family DNA polymerasesGil 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... - Exploring the energy landscape of antibody-antigen complexes: protein dynamics, flexibility, and molecular recognitionMegan 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... - Direct and high resolution characterization of cytochrome c equilibrium foldingLaura 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... - Flexibility and molecular recognition in the immune systemRalph 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... - Polymerase recognition of unnatural base pairsChengzhi 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 - Antibody evolution constrains conformational heterogeneity by tailoring protein dynamicsJörg 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... - Type I signal peptidase and protein secretion in Staphylococcus epidermidisMichael E Powers
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
J Bacteriol 193:340-8. 2011.... - In vitro activities of arylomycin natural-product antibiotics against Staphylococcus epidermidis and other coagulase-negative staphylococciPeter 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... - Protein dynamics and cytochrome c: correlations between ligand vibrations and redox activityJodie 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... - Polymerase evolution: efforts toward expansion of the genetic codeAaron 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... - Transcription of an expanded genetic alphabetYoung 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... - Substituent effects on the pairing and polymerase recognition of simple unnatural base pairsGil 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... - Optimization of unnatural base pair packing for polymerase recognitionShigeo 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... - Role of Doa1 in the Saccharomyces cerevisiae DNA damage responseEwa 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... - An efficiently extended class of unnatural base pairsAaron 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... - Pph3-Psy2 is a phosphatase complex required for Rad53 dephosphorylation and replication fork restart during recovery from DNA damageBryan 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... - Structural and initial biological analysis of synthetic arylomycin A2Tucker 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... - Discovery, characterization, and optimization of an unnatural base pair for expansion of the genetic alphabetAaron 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... - Carbon-deuterium bonds as probes of dihydrofolate reductaseMegan 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.... - Efforts towards expansion of the genetic alphabet: pyridone and methyl pyridone nucleobasesAaron M Leconte
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
Angew Chem Int Ed Engl 45:4326-9. 2006 - Stability and polymerase recognition of pyridine nucleobase analogues: role of minor-groove H-bond acceptorsYoonkyung 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 - Differential solvation and tautomer stability of a model base pair within the minor and major grooves of DNAFrancois 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... - Chemical biology: a broader take on DNAAaron M Leconte
Nature 444:553-5. 2006 - Side effects may include evolutionRyan T Cirz
Nat Med 12:890-1. 2006 - Amplify this! DNA and RNA get a third base pairAaron M Leconte
Nat Methods 3:667-8. 2006 - Infrared line shape of an alpha-carbon deuterium-labeled amino acidCarrie 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 Grants
- Expanding the Genetic Alphabet by Design and SelectionFLOYD ROMESBERG; Fiscal Year: 2009..Figure 1. The d5SICS:dNaM base pair ..
- Evolving Novel Polymerases for Genome SequencingFLOYD ROMESBERG; Fiscal Year: 2007....
- Expanding the Genetic Alphabet by Design and SelectionFLOYD 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. ..
- Pathways Controlling Genome Stability and MutationFLOYD 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. ..
- EXPANDING THE GENETIC ALPHABET BY POLYMERASE EVOLUTIONFLOYD 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. ..
- Expanding the Genetic Alphabet by Design and SelectionFloyd E Romesberg; Fiscal Year: 2010..Figure 1. The d5SICS:dNaM base pair ..