Systems biology of the structural proteome

被引:42
作者
Brunk, Elizabeth [1 ,2 ]
Mih, Nathan [3 ]
Monk, Jonathan [1 ]
Zhang, Zhen [1 ]
O'Brien, Edward J. [1 ,3 ,4 ]
Bliven, Spencer E.
Chen, Ke [1 ]
Chang, Roger L. [5 ]
Bourne, Philip E. [6 ]
Palsson, Bernhard O. [1 ]
机构
[1] Univ Calif La Jolla, Dept Bioengn, San Diego, CA 92093 USA
[2] Joint BioEnergy Inst, Emeryville, CA 94608 USA
[3] Univ Calif La Jolla, Bioinformat & Syst Biol Program, San Diego, CA 92093 USA
[4] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA
[5] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA
[6] NIH, Off Director, Bethesda, MD 20894 USA
基金
美国国家卫生研究院; 瑞士国家科学基金会;
关键词
COMPLETE GENOME SEQUENCE; I-TASSER; STRUCTURE PREDICTION; METABOLIC NETWORK; PROTEINS; EVOLUTION; DATABASE; RECONSTRUCTION; RECOGNITION; EFFICIENT;
D O I
10.1186/s12918-016-0271-6
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: The success of genome-scale models (GEMs) can be attributed to the high-quality, bottom-up reconstructions of metabolic, protein synthesis, and transcriptional regulatory networks on an organism-specific basis. Such reconstructions are biochemically, genetically, and genomically structured knowledge bases that can be converted into a mathematical format to enable a myriad of computational biological studies. In recent years, genome-scale reconstructions have been extended to include protein structural information, which has opened up new vistas in systems biology research and empowered applications in structural systems biology and systems pharmacology. Results: Here, we present the generation, application, and dissemination of genome-scale models with protein structures (GEM-PRO) for Escherichia coli and Thermotoga maritima. We show the utility of integrating molecular scale analyses with systems biology approaches by discussing several comparative analyses on the temperature dependence of growth, the distribution of protein fold families, substrate specificity, and characteristic features of whole cell proteomes. Finally, to aid in the grand challenge of big data to knowledge, we provide several explicit tutorials of how protein-related information can be linked to genome-scale models in a public GitHub repository (https://github.com/SBRG/GEMPro/tree/master/GEMPro_recon/). Conclusions: Translating genome-scale, protein-related information to structured data in the format of a GEM provides a direct mapping of gene to gene-product to protein structure to biochemical reaction to network states to phenotypic function. Integration of molecular-level details of individual proteins, such as their physical, chemical, and structural properties, further expands the description of biochemical network-level properties, and can ultimately influence how to model and predict whole cell phenotypes as well as perform comparative systems biology approaches to study differences between organisms. GEM-PRO offers insight into the physical embodiment of an organism's genotype, and its use in this comparative framework enables exploration of adaptive strategies for these organisms, opening the door to many new lines of research. With these provided tools, tutorials, and background, the reader will be in a position to run GEM-PRO for their own purposes.
引用
收藏
页数:16
相关论文
共 113 条
[1]   Structural systems biology: modelling protein interactions [J].
Aloy, P ;
Russell, RB .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2006, 7 (03) :188-197
[2]  
[Anonymous], BIOTECHNIQU IN PRESS
[3]  
[Anonymous], NAT ACAD SCI
[4]  
[Anonymous], STRUCTURAL EVOLUTION
[5]  
[Anonymous], RCSB PDB DRUG PDB ID
[6]  
[Anonymous], SCI REP
[7]  
[Anonymous], PYTHON DATA ANAL DAT
[8]   Closed structure of phosphoglycerate kinase from Thermotoga maritima reveals the catalytic mechanism and determinants of thermal stability [J].
Auerbach, G ;
Huber, R ;
Grattinger, M ;
Zaiss, K ;
Schurig, H ;
Jaenicke, R ;
Jacob, U .
STRUCTURE, 1997, 5 (11) :1475-1483
[9]   ProDy: Protein Dynamics Inferred from Theory and Experiments [J].
Bakan, Ahmet ;
Meireles, Lidio M. ;
Bahar, Ivet .
BIOINFORMATICS, 2011, 27 (11) :1575-1577
[10]   Engineering specialized metabolic pathways-is there a room for enzyme improvements? [J].
Bar-Even, Arren ;
Tawfik, Dan Salah .
CURRENT OPINION IN BIOTECHNOLOGY, 2013, 24 (02) :310-319