Structural genomics: A pipeline for providing structures for the biologist

  title={Structural genomics: A pipeline for providing structures for the biologist},
  author={Mark R. Chance and Anne R Bresnick and Stephen K. Burley and Jianrong Jiang and Christopher D. Lima and Andrej Sali and Steven C. Almo and Jeffrey B. Bonanno and John A Buglino and Simon J. Boulton and Hua Chen and Narayanan Eswar and Guoshun He and Raymond Y Huang and Valentin A. Ilyin and Linda McMahan and Ursula Pieper and Soumya S. Ray and Marc Vidal and Li Kai Wang},
  journal={Protein Science},
Progress in understanding the organization and sequences of genes in model organisms and humans is rapidly accelerating. Although genome sequences from prokaryotes have been available for some time, only recently have the genome sequences of several eukaryotic organisms been reported, including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis thaliana, and humans (Green 2001). A logical continuation of this line of scientific inquiry is to understand the… 

CHAPTER 1 Overview of Mass Spectrometry Technologies for Examining Protein Structure : Current and Future Directions

The fundamental contributions of mass spectrometry to structural biology studies have grown dramatically due to increases in instrument sensitivity and resolution that have accrued over the past 10 years, which has advanced the ability to reliably sequence and identify protein.

High-throughput computational and experimental techniques in structural genomics.

The Consortium has established a pipeline for structural biology studies, automated modeling of ORF sequences using solved (template) structures, and a novel high-throughput approach (metallomics) to examining the metal binding to purified protein targets, and some of the experimental and bioinformatics efforts leading to structural annotation of proteins.

Predictionof protein function fromprotein sequenceandstructure

The state of the art in function prediction is reviewed and the use of protein–protein interaction patterns, and correlations between occurrences of related proteins in different organisms, as indicators of functional properties are described.

High-throughput expression of C. elegans proteins.

This protein expression effort has investigated the largest number of genes in any organism to date, and bioinformatics analysis of the data indicates that protein hydrophobicity is a key determining factor for an ORF to yield a soluble expression product.

Structural genomics and the Protein Data Bank

Comprehensive genome analysis of 203 genomes provides structural genomics with new insights into protein family space

It is shown that the structural genomics initiatives should aim to provide structures for less than a thousand structurally uncharacterized Pfam families to achieve reasonable structural annotation of the genomes, and that 67% of eukaryotic sequences are multi-domain compared with 56% of sequences in prokaryotes.

Characterization of protein structure and function at genome scale with a computational prediction pipeline.

Development of new computational tools for interpretation of large quantity of genomic sequence data for structural and functional inference and example applications of these tools to studies of microbial genomes, particularly cyanobacterialgenomes are focused on.

Structural genomics – expanding protein structural universe

New high-throughput technologies supported by robotics and automation in molecular biology, protein expression, purification, crystallization, and structure determination are being disseminated to the public and, therefore, contribute to the acceleration of new discoveries in biology.

Structural proteomics of minimal organisms: Conservation of protein fold usage and evolutionary implications

It is found that proteins performing essential cellular functions closely related to transcription and translation exhibit a higher degree of conservation in fold usage than proteins in other functional categories.



Structural genomics: beyond the Human Genome Project

A program of high-throughput X-ray crystallography aimed at developing a comprehensive mechanistic understanding of normal and abnormal human and microbial physiology at the molecular level is about to embark on.

Interrelating different types of genomic data, from proteome to secretome: 'oming in on function.

The term "translatome" is suggested to describe the members of the proteome weighted by their abundance, and the "functome" to describe all the functions carried out by these in the cellular contents of the genome.

GATEWAY recombinational cloning: application to the cloning of large numbers of open reading frames or ORFeomes.

Protein Structure Prediction and Structural Genomics

This Viewpoint begins by describing the essential features of the methods, the accuracy of the models, and their application to the prediction and understanding of protein function, both for single proteins and on the scale of whole genomes.

Large-scale protein structure modeling of the Saccharomyces cerevisiae genome.

  • R. SánchezA. Sali
  • Biology, Engineering
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
The fold assignment, comparative protein structure modeling, and model evaluation were automated completely and resulted in all-atom 3D models for substantial segments of 1,071 of the yeast proteins, only 40 of which have had their 3D structure determined experimentally.

Constructing multigenome views of whole microbial genomes.

A system to carry out cross-genome comparisons of open reading frames (ORFs) from multiple genomes and a genome profiling system that allows to explore pairwise comparisons at different levels of match similarity and ask biologically motivated queries involving number and identity of ORFs.

A protein–protein interaction map of the Caenorhabditis elegans 26S proteasome

A two‐hybrid‐based protein interaction map was generated and novel potential proteasome interactors were identified, including an E3 ubiquitin ligase, transcription factors, chaperone proteins and other proteins not yet functionally annotated.

Comparative protein structure modeling of genes and genomes.

There is a need to develop an automated, rapid, robust, sensitive, and accurate comparative modeling pipeline applicable to whole genomes and to encourage new kinds of applications for the many resulting models, based on their large number and completeness at the level of the family, organism, or functional network.

Combined Functional Genomic Maps of the C. elegans DNA Damage Response

A strategy that combines protein-protein interaction mapping and large-scale phenotypic analysis in Caenorhabditis elegans identified 12 worm DDR orthologs and 11 novel DDR genes, including a putative ortholog of hBCL3, a gene frequently altered in chronic lymphocytic leukemia.

Protein interaction mapping in C. elegans using proteins involved in vulval development.

A protein interaction mapping project is now feasible for C. elegans on a genome-wide scale and should contribute to the understanding of molecular mechanisms in this organism and in human diseases.