Search results for "genomics"

Protein NMR Structures Refined with Rosetta Have Higher Accuracy Relative to Corresponding X-ray Crystal Structures

2014

We have found that refinement of protein NMR structures using Rosetta with experimental NMR restraints yields more accurate protein NMR structures than those that have been deposited in the PDB using standard refinement protocols. Using 40 pairs of NMR and X-ray crystal structures determined by the Northeast Structural Genomics Consortium, for proteins ranging in size from 5-22 kDa, restrained Rosetta refined structures fit better to the raw experimental data, are in better agreement with their X-ray counterparts, and have better phasing power compared to conventionally determined NMR structures. For 37 proteins for which NMR ensembles were available and which had similar structures in solu…

Evaluating protein structures determined by structural genomics consortia.

2006

Structural genomics projects are providing large quantities of new 3D structural data for proteins. To monitor the quality of these data, we have developed the protein structure validation software suite (PSVS), for assessment of protein structures generated by NMR or X-ray crystallographic methods. PSVS is broadly applicable for structure quality assessment in structural biology projects. The software integrates under a single interface analyses from several widely-used structure quality evaluation tools, including PROCHECK (Laskowski et al., J Appl Crystallog 1993;26:283-291), MolProbity (Lovell et al., Proteins 2003;50:437-450), Verify3D (Luthy et al., Nature 1992;356:83-85), ProsaII (Si…

A new evolutionary paradigm for the Parkinson disease gene DJ-1.

2006

The DJ-1 gene is extensively studied because of its involvement in familial Parkinson disease. DJ-1 belongs to a complex superfamily of genes that includes both prokaryotic and eukaryotic representatives. We determine that many prokaryotic groups, such as proteobacteria, cyanobacteria, spirochaetes, firmicutes, or fusobacteria, have genes, often incorrectly called "Thij," that are very close relatives of DJ-1, to the point that they cannot be clearly separated from the eukaryotic DJ-1 genes by phylogenetic analyses of their sequences. In addition, and contrary to a previous study that suggested that DJ-1 genes were animal specific, we show that DJ-1 genes are found in at least 5 of the 6 ma…

Assessing model accuracy using the homology modeling automatically software

2007

Homology modeling is a powerful technique that greatly increases the value of experimental structure determination by using the structural information of one protein to predict the structures of homologous proteins. We have previously described a method of homology modeling by satisfaction of spatial restraints (Li et al., Protein Sci 1997;6:956-970). The Homology Modeling Automatically (HOMA) web site,http://www-nmr.cabm.rutgers.edu/HOMA, is a new tool, using this method to predict 3D structure of a target protein based on the sequence alignment of the target protein to a template protein and the structure coordinates of the template. The user is presented with the resulting models, togeth…

Pharmacokinetics in Drug Discovery

2007

The aim of this current review is to summarize the present status of pharmacokinetics in Drug Discovery. The review is structured into four sections. The first section is a general overview of what we understand by pharmacokinetics and the different LADMET aspects: Liberation, Absorption, Distribution, Metabolism, Excretion, and Toxicity. The second section highlights the different computational or in silico approaches to estimate/predict one or several aspects of the pharmacokinetic profile of a discovery lead compound. The third section discusses the most commonly used in vitro methodologies. The fourth and last section examines the various approaches employed towards the pharmacokinetic …

NMR structure of hypothetical protein TA0938 from Thermoplasma acidophilum.

2007

Metagenomics uncovers a new group of low GC and ultra-small marine Actinobacteria

2013

We describe a deep-branching lineage of marine Actinobacteria with very low GC content (33%) and the smallest free living cells described yet (cell volume ca. 0.013 μm(3)), even smaller than the cosmopolitan marine photoheterotroph, 'Candidatus Pelagibacter ubique'. These microbes are highly related to 16S rRNA sequences retrieved by PCR from the Pacific and Atlantic oceans 20 years ago. Metagenomic fosmids allowed a virtual genome reconstruction that also indicated very small genomes below 1 Mb. A new kind of rhodopsin was detected indicating a photoheterotrophic lifestyle. They are estimated to be ~4% of the total numbers of cells found at the site studied (the Mediterranean deep chloroph…

Comparative genomic sequencing reveals a strikingly similar architecture of a conserved syntenic region on human chromosome 11p15.3 (including gene S…

2001

Comparative genomics is a superior way to identify phylogenetically conserved features like genes or regions involved in gene regulation. The comparison of extended orthologous chromosomal regions should also reveal other characteristic traits essential for chromosome or gene function. In the present study we have sequenced and compared a region of conserved synteny from human chromosome 11p15.3 and mouse chromosome 7. In human, this region is known to contain several genes involved in the development of various disorders like Beckwith-Wiedemann overgrowth syndrome and other tumor diseases. Furthermore, in the neighboring chromosome region 11p15.5 extensive imprinting of genes has been repo…

Functional and genetic deconstruction of the cellular origin in liver cancer.

2015

During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, w…

Primate Cytogenetics and Comparative Genomics

2006

This volume is a collection of contributions of a Florentine post congress symposium on "Primate Cytogenetics and Comparative Genomics" held on occasion of the XX International Primatological Congress (Turin in 2004). Comparative Molecular Cytogenetics and Genomics are two rapidly expanding fields. Researchers from Italy, Germany, Spain, United States and Japan meet in Florence to discuss over a two day period recent advances and summarize the current state of the science.