Structural bioinformatics

Structural bioinformatics is the branch of bioinformatics which is related to the analysis and prediction of the three-dimensional structure of biological macromolecules such as proteins, RNA, and DNA. It deals with generalizations about macromolecular 3D structure such as comparisons of overall folds and local motifs, principles of molecular folding, evolution, and binding interactions, and structure/function relationships, working both from experimentally solved structures and from computational models. The term structural has the same meaning as in structural biology, and structural bioinformatics can be seen as a part of computational structural biology.

Overview

Informatics approaches used in structural bioinformatics are

Selection of Target - Potential targets are identified by comparing them with databases of known structures and sequence. The importance of a target can be decided on the basis of published literature. Target can also be selected on the basis of its protein domain. Protein domain are building blocks that can be rearranged to form new proteins. They can be studied in isolation initially.
Tracking X-ray crystallography trials - X-Ray crystallography can be used to reveal three-dimensional structure of a protein. But, in order to use X-ray for studying protein crystals, pure proteins crystals must be formed, which can take a lot of trials. This leads to a need for tracking the conditions and results of trials. Furthermore, supervised machine learning algorithms can be used on the stored data to identify conditions that might increase the yield of pure crystals.
Analysis of X-Ray crystallographic data - The diffraction pattern obtained as a result of bombarding X-rays on electrons is Fourier transform of electron density distribution. There is a need for algorithms that can deconvolve Fourier transform with partial information ( due to missing phase information, as the detectors can only measure amplitude of diffracted X-rays, and not the phase shifts ). Extrapolation technique such as Multiwavelength anomalous dispersion can be used to generate electron density map, which uses the location of selenium atoms as a reference to determine rest of the structure. Standard Ball-and-stick model is generated from the electron density map.
Analysis of NMR spectroscopy data - Nuclear magnetic resonance spectroscopy experiments produce two (or higher) dimensional data, with each peak corresponding to a chemical group within the sample. Optimization methods are used to convert spectra into three dimensional structures.
Correlating Structural information with functional information - Structural studies can be used as probe for structural-functional relationship.

References

Books

Bourne, P.E., and Gu, J. (2009) Structural Bioinformatics (2nd edition), John Wiley & Sons, New York, ISBN 978-0-470-18105-8
Bourne, P.E., and Weissig, H. (2003) Structural Bioinformatics, Wiley ISBN 0-471-20199-5
Leach, Andrew (2001) Molecular Modelling: Principles and Applications (2nd edition), Prentice Hall, ISBN 978-0-582-38210-7
Peitsch, M.C., and Schwede, T. (2008) Computational Structural Biology: Methods and Applications World Scientific, ISBN 978-9812778772

Hallmark publications

Leontis NB, Westhof E (2001). "Geometric nomenclature and classification of RNA base pairs". RNA. 7 (4): 499–512. doi:10.1017/S1355838201002515. PMC 1370104. PMID 11345429.
Richardson JS (1981). "The anatomy and taxonomy of protein structure". Adv Protein Chem. Advances in Protein Chemistry. 34: 167–339. doi:10.1016/S0065-3233(08)60520-3. ISBN 978-0-12-034234-1. PMID 7020376.
Ramachandran GN, Sasisekharan V (1968). "Conformation of polypeptides and proteins". Adv Protein Chem. Advances in Protein Chemistry. 23: 283–438. doi:10.1016/S0065-3233(08)60402-7. ISBN 978-0-12-034223-5. PMID 4882249.
Ramachandran GN, Ramakrishnan C, Sasisekharan V (1963). "Stereochemistry of polypeptide chain configurations". J Mol Biol. 7: 95–9. doi:10.1016/S0022-2836(63)80023-6. PMID 13990617.

External links

Databases

MMDB Experimentally determined three-dimensional structures of biomolecules derived from Protein Data Bank (PDB) [1]
Protein Data Bank (PDB) Three-dimensional structural data of proteins and nucleic acids
Nucleic acid Data Base (NDB) Experimentally determined information about nucleic acids (DNA, RNA)
Structural Classification of Proteins (SCOP) Comprehensive description of the structural and evolutionary relationships between structurally known proteins
TOPOFIT-DB Protein structural alignments based on the TOPOFIT method [2]
Electron Density Server (EDS) Electron-density maps and statistics about the fit of crystal structures and their maps
CASP Prediction Center Community-wide, worldwide experiment for protein structure prediction CASP
PISCES server for creating non-redundant lists of proteins Generates PDB list by sequence identity and structural quality criteria
The Structural Biology Knowledgebase Tools to aid in protein research design
ProtCID: The Protein Common Interface Database Database of similar protein-protein interfaces in crystal structures of homologous proteins

Software

Molecular Operating Environment (MOE) Extensive platform including structural modelling for proteins, protein families and antibodies
SBL The Structural Bioinformatics Library: end-user applications and advanced algorithms
BALLView molecular modeling and visualization
FRIEND visualization and analysis
STING visualization and analysis
PyMOL viewer and modeling
VMD viewer, molecular dynamics
KiNG, an open-source Java kinemage viewer
MolMol viewer, NMR
SPDBV DeepView viewer
STRIDE determination of secondary structure from coordinates
MolProbity structure-validation web server
PROCHECK, a structure-validation web service
CheShift, a protein structure-validation on-line application
MolTalk, structural bioinformatics software
Jmol, a molecular viewer Java applet with rasmol-like scripting capabilities and Javascript interaction
PROPKA, rapid prediction of protein pKa values based on empirical structure/function relationships
CARA – Computer Aided Resonance Assignment
Docking Server, a molecular docking web server
StarBiochem, a java protein viewer, features direct search of protein databank
Biskit, a python platform for structural bioinformatics
SPADE the structural proteomics application development environment
UGENE, an opensource multiplatform viewer for PDB and MMDB files
PocketSuite, a web portal for various web-servers for binding site level analysis
MSL, an open-source C++ molecular modeling software library for the implementation of structural analysis, prediction and design methods
PSSpred – Protein secondary structure prediction

v t e Genomics
Fields	Cognitive genomics Computational genomics Comparative genomics Functional genomics Genome project Human Genome Project Metagenomics Human Microbiome Project Pangenomics Personal genomics Population genomics Sociogenomics Structural genomics
Bioinformatics	Biochip Cheminformatics Chemogenomics Connectomics Human Connectome Project Epigenomics Human Epigenome Project Glycomics Immunomics Lipidomics Metabolomics Microbiomics Nutrigenomics Paleopolyploidy Pharmacogenetics Pharmacogenomics Systems biology Toxicogenomics Transcriptomics
Structural biology	Proteomics Human proteome project Call-map proteomics Structure-based drug design Expression proteomics
Research tools	2-D electrophoresis Mass spectrometer Electrospray ionization Matrix-assisted laser desorption ionization Matrix-assisted laser desorption ionization-time of flight mass spectrometer Microfluidic-based tools Isotope affinity tags Chromosome conformation capture
Organizations	DNA Data Bank of Japan (JP) European Molecular Biology Laboratory (EU) National Institutes of Health (USA) Wellcome Sanger Institute (UK)
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