We do research in bioinformatics. Broadly, we are interested in large-scale analyses of the rapidly expanding number of genome sequences and macromolecular structures. It is hoped that these will allow us to address a number of overall, statistical questions about proteins, relating to their physical properties, cellular function, and phylogenetic distribution, More specifically, we have two research foci. The first is comparative genomics. We compare genomes in terms of protein folds, biochemical pathways, and patterns of gene expression. We are also developing methods to cluster proteins into fold families and predict structure and function from sequence similarity. The second focus is the analysis of macromolecular geometry. Here we concentrate on the relationship between packing and motions and try to find standardized ways to describe conformational variability. Again the work is performed in a database framework, through comparison of solved structures. We are collaborating with many members of the CSB. We are working with D Engelman (i) on the prediction and identification of membrane proteins, (ii) on surveying membrane protein dimerization motifs, and (iii) on the analysis of packing in membrane proteins. We are working with P Moore and T Steitz on the analysis of packing in RNA structures. We are also working with T Steitz on the analysis of specific macromolecular motions. We are working with L Regan on biophysically characterizing the structurally uncharacterized proteins in eukaryotic genomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM022778-33
Application #
7591168
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
33
Fiscal Year
2008
Total Cost
$488,573
Indirect Cost
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Greenlee, Etienne B; Stav, Shira; Atilho, Ruben M et al. (2018) Challenges of ligand identification for the second wave of orphan riboswitch candidates. RNA Biol 15:377-390
Mirihana Arachchilage, Gayan; Sherlock, Madeline E; Weinberg, Zasha et al. (2018) SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches. RNA Biol 15:371-378
Wang, Jimin (2018) Determination of chemical identity and occupancy from experimental density maps. Protein Sci 27:411-420
Sherlock, Madeline E; Sudarsan, Narasimhan; Breaker, Ronald R (2018) Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems. Proc Natl Acad Sci U S A 115:6052-6057
Harris, Kimberly A; Breaker, Ronald R (2018) Large Noncoding RNAs in Bacteria. Microbiol Spectr 6:
Yang, Yang; Kang, Dongwei; Nguyen, Laura A et al. (2018) Structural basis for potent and broad inhibition of HIV-1 RT by thiophene[3,2-d]pyrimidine non-nucleoside inhibitors. Elife 7:
Wang, Jimin; Liu, Zheng; Crabtree, Robert H et al. (2018) On the damage done to the structure of the Thermoplasma acidophilum proteasome by electron radiation. Protein Sci 27:2051-2061
Sherlock, Madeline E; Sadeeshkumar, Harini; Breaker, Ronald R (2018) Variant Bacterial Riboswitches Associated with Nucleotide Hydrolase Genes Sense Nucleoside Diphosphates. Biochemistry :
Harris, Kimberly A; Zhou, Zhiyuan; Peters, Michelle L et al. (2018) A second RNA-binding protein is essential for ethanol tolerance provided by the bacterial OLE ribonucleoprotein complex. Proc Natl Acad Sci U S A 115:E6319-E6328
Li, Sanshu; Breaker, Ronald R (2017) Identification of 15 candidate structured noncoding RNA motifs in fungi by comparative genomics. BMC Genomics 18:785

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