Structural Bioinformatics Main resource on the web: PDB History Kind of data How to search

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1 Protein Data Bank Protein Data Bank Structural Bioinformatics Main resource on the web: PDB History Kind of data How to search Goal Be able of searching and understanding structural information which is available at the PDB 1

2 Structural Bioinformatics Creation of general purpose methods for manipulating information about biological macromolecules, and Application of these methods to solving problems in Biology and creating new knowledge. Protein Data Bank Single worldwide repository for the processing and distribution of 3D biological macromolecular structure data 2

3 Protein Data Bank Created in 1971 by Brookhaven National Laboratory Since 1998 is maintained by Research Collaboratory for Structural Bioinformatics (RCSB) Contains more than structures Origin: X-ray crystallography, NMR, and electron microscopy 3

4 PDB content growth protein structures PDB content 4

5 PDB file description PDBid: nxyz HEADER Chemical and biochemical features Experimental details of the structure determination Some structural features COORDINATES Atomic coordinates of the structure PDB file description (II) All files: Source Sequence Chemical structure if cofactors and prostetic groups Name of all components of the structure Qualitative description of the characteristics of the structure Literature citations Three-dimensional coordinates 5

6 PDB file description (III) Additional items for X-ray structure determinations: Crystallization conditions Crystallographic data Data collection information Data collection statistics Refinement information: resolution Temperature factor and occupancies assigned to each atom PDB file description (IV) Additional items for NMR structure determinations: Number of models deposited and if one should be designated as representative Data collection information Sample conditions Experimental conditions Constraint file used to derived the structure 6

7 Formats PDB format mmcif: a dictionary-based approach XML 7

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9 Data acquisition and processing Fully documented and integrated data processing system: Data deposition Annotation Validation Distribution 9

10 Data access FTP access Search the archive 10

11 Search the archive PDBid or keywords Author Advanced 11

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13 Search the archive (II) Problema Transtiretina (TTR), es una proteína tetrámerica cuya desnaturalización es la causante de una enfermedad degenerativa denominada amiloidosis sistémica senil. La mayoría de las mutaciones son amiloidogénicas, es decir, aceleran la aparición de la enfermedad. Una de las estrategias terapéuticas consiste en diseñar compuestos que se unan a TTR y estabilicen el tetrámero. 13

14 Problema Qué información estructural hay sobre la proteína nativa? Qué información estructural hay sobre las proteínas mutadas? Existe información estructural sobre complejos con ligandos que potencialmente protejan de la enfermedad? 14

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23 Bibliography Bourne PE, Weissing H (eds) Structural bioinformatics. Hoboken (NJ): Wiley-Liss Inc, 2003 Kouranov A, Xie L, de la Cruz J, Chen L, Westbrook J, Bourne PE, Berman HM. The RCSB PDB information portal for structural genomics. Nucleic Acids Res. 2006;34(Database issue):d