复旦大学生命科学学院：《蛋白质组学》Structural proteomics

Part v Structural Proteomics 0/27/2005 Chaoqun Wu, Fudan University

10/27/2005 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 1 Part VI. Structural Proteomics

Structural proteomics Structural proteomics has the goal of obtaining useful, three-dimensional models of all proteins by a combina- tion of experimental structure determination and comparative model building 0/27/2005 Chaoqun Wu, Fudan University

10/27/2005 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 2 Structural proteomics Structural proteomics Structural proteomics has the goal of obtaining useful, three-dimensional models of all proteins by a combina￾tion of experimental structure determination and comparative model building. Structural proteomics has the goal of obtaining useful, three-dimensional models of all proteins by a combina￾tion of experimental structure determination and comparative model building

Computation Cellular Developmental Morphogenesis and Developm ent Signal Transduction P athways Bio chemical Path叫ays Predicting Catalysis, Molecular/ Structures of Mult Experiments redidting Effects of m RNAc. and othe Prediding Three-Dimensional Predicting Functions Biome locule Structures ofp rote ins and RNAs Predictng Protein Simulating and Understanding Gene Expression Networks Reconstructing Phylogeny Genome Large- scale \Genes and Gene Structures Homology, and Comparitive equenc Assem bled Genomes Sequence variation of The experimental (left and computational (right) hierarchies will increasingly become codependent as the research community models greater biological complexity 0/27/2005 Chaoqun Wu, Fudan University

10/27/2005 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 3 The experimental (left) and computational (right) hierarchies will increasingly become codependent as the research community models greater biological complexity. The experimental (left) and computational (right) hierarchies will increasingly become codependent as the research community models greater biological complexity

Genome Sequencing Projects Cell Microorganism Target s Selection PDB Database 0 0 HT Crystallography and NMr Functional Studies Structural genomics Drug Development Metabolic Pathways Structure+ Function ew Family mem bers Characterization New Folds Homology Modeling Global structural genomics efforts will be major players in Completing the protein family and fold landscape 0/27/2005 haoqun Wu, Fudan University

10/27/2005 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 4 Global structural genomics efforts will be major players in Completing the protein family and fold landscape. Global structural genomics efforts will be major players in Completing the protein family and fold landscape

Table 1 List of pilot projects in structural genomics Pilot project organizers Organism SBurley, A Sali, J. Sussman S cerevisiae A. Edwards M. thermoautotrophicum D. Eisenberg, T. Terwilliger P aerophilum S,-H. Kim M. janaschii G. Montelione, S Anderson Metazoa Moult H influenzae S Yokoyama T Thermophilus, HB8 These projects were described at the meeting. Each project gen erally involves several independent laboratories. Only speakers at the meeting are listed in the first column Their addresses can be foundathttp://lion.cabm.rutgersedw/bioinformatics_meeting 0/27/2005 Chaoqun Wu, Fudan University

10/27/2005 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 5

It is feasible to determine at least 10,000 protein structures within the next five years No new discoveries or methods are needed for this task The average cost per structure is expected to decrease significantly from $200,000 per structure to perhaps less than $20,000 per structure 0/27/2005 Chaoqun Wu, Fudan University

10/27/2005 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 6 It is feasible to determine at least 10,000 protein structures within the next five years. No new discoveries or methods are needed for this task. The average cost per structure is expected to decrease significantly from $200,000 per structure to perhaps less than $20,000 per structure

多 庭端静 Large-scale protein structure modeling A small sample of the 1, 100 comparative models calculated for the proteins in the yeast genome is displayed over an image of a yeast cel

10/27/2005 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 7 Large-scale protein structure modeling. A small sample of the 1,100 comparative models calculated for the proteins in the yeast genome is displayed over an image of a yeast cell

Experimental structure determination 蛋白质的 体外翻译 蛋自质的生选择性蛋白质 物活性检测入分子的突变 0/27/2005 Chaoqun Wu, Fudan University

10/27/2005 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 8 Experimental structure determination 蛋白质的生 物活性检测 选择性蛋白质 分子的突变 蛋白质的 体外翻译

1. Target selection(Grouping The targets for structure determination will be 1.Individual domains rather than multi-domain proteins(Chris Sander, Millenium Information 2. Easier to determine by X-ray crystallography or NMR spectroscopy than the more flexible multi domain proteins 3. Done by pairwise comparison of all protein sequences, followed by clustering into groups of domains 4. The representatives of the groups without structurally defined members 5. Members that share at least 30% sequence identity (30-seq families), rather than those that correspond to superfamiles or fold families 0/27/2005 Chaoqun Wu, Fudan University

10/27/2005 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 9 1. Target selection (Grouping) The targets for structure determination will be 1. Individual domains rather than multi-domain proteins (Chris Sander, Millenium Information). 2. Easier to determine by X-ray crystallography or NMR spectroscopy than the more flexible multi￾domain proteins. 3. Done by pairwise comparison of all protein sequences, followed by clustering into groups of domains. 4. The representatives of the groups without structurally defined members. 5. Members that share at least 30% sequence identity (30-seq families), rather than those that correspond to superfamiles or fold families. The targets for structure determination will be 1. Individual domains rather than multi-domain proteins (Chris Sander, Millenium Information). 2. Easier to determine by X-ray crystallography or NMR spectroscopy than the more flexible multi￾domain proteins. 3. Done by pairwise comparison of all protein sequences, followed by clustering into groups of domains. 4. The representatives of the groups without structurally defined members. 5. Members that share at least 30% sequence identity (30-seq families), rather than those that correspond to superfamiles or fold families

A variety of different criteria likely will be used for this task; for example ■ size of the family, biological knowledge about the family, distribution of the members among various organIsms, the pharmaceutical relevance the likelihood of a successful structure determination and so forth 0/27/2005 Chaoqun Wu, Fudan University

10/27/2005 Chaoqun Wu, Fudan University Chaoqun Wu, Fudan University 10 A variety of different criteria likely will be used for this task; for example: „ size of the family, „ biological knowledge about the family, „ distribution of the members among various organisms, „ the pharmaceutical relevance, „ the likelihood of a successful structure determination, and so forth . A variety of different criteria likely will be used for this task; for example: „ size of the family, „ biological knowledge about the family, „ distribution of the members among various organisms, „ the pharmaceutical relevance, „ the likelihood of a successful structure determination, and so forth