Searching and Analysing 3D Protein-ligand Structures using PDBe web services. Abhik Mukhopadhyay.

Transcription

1 Searching and Analysing 3D Protein-ligand Structures using PDBe web services Abhik Mukhopadhyay www.

2 About wwpdb and PDBe PDBe web services Searching PDBe A case study Validation of Protein ligand structures

3 What is the Protein Data Bank (PDB)? An archive of experimentally determined 3-dimensional structures of biological macromolecules Protein, nucleic acids, small molecules Available to anyone for free

4 The PDB FTP Archive wwpdb.org

5 Value added data Value added data Value added data Value added data The PDB FTP Archive wwpdb.org

6 PDB growth over time wwpdb.org X-ray EM NMR

7 Methods of solving the structures 88% X-ray crystallography 10% NMR Spectroscopy 1% Electron microscopy wwpdb.org

8 What is PDB? PDBe tools and services Searching PDBe A case study Validation of Protein ligand structures

9 PDBe tools and services

10 PDBe tools and services

11 PDBe tools and services Search bar

12 Latest PDB statistics

13 Latest PDB statistics

14 PDBe tools and services

15 PDBe tools and services

16 PDBe tools and services - PDBeChem /chem

17 Chemical component dictionary Contains over 26,329 unique chemical components (amino acids/nucleotides, small molecule ligands, solvents..) For each unique chemical component: Unique 3 letter code Name, systematic & synonym Chemical formula AMODIAQUINE CQA SMILES, InChI Stereo configuration of atoms and bonds in cases of stereo-isomers (R/S E/Z) Ideal and representative 3D coordinates /chem

18 PDBe tools and services - PDBeChem /chem

19 PDBe tools and services - PDBeChem /chem

20 PDBe tools and services - PDBeChem /chem

21 PDBe tools and services - PDBeChem /chem

22 PDBe tools and services - PDBeChem /chem

23 PDBe tools and services - PDBeChem /chem

24 PDBe tools and services - PDBeChem /chem

25 PDBe tools and services - PDBeChem /chem

26 Accessing chemistry related information using REST-API What hetcode present in entry Information about hetcode Functional annotation, and mapping

27 PDBe REST-API Designed to provide programmatic access to all information in the PDBe database For easy access, the API contains separate modules API also makes it possible to access structure-related information in manageable data blocks /api

28 PDBe REST-API

29 Other popular PDBe services PDBeFold comparison and 3D alignment of protein structures examination of a protein structure for structure based similarity with the whole PDB /fold

30 Other popular PDBe services PDBePISA Tool to investigate formation of macromolecular interfaces and stability Retrieve pre-calculated results for the whole PDB archive. /pisa

31 SIFTS /sifts

32 What is PDB? PDBe tools and services Searching PDBe A case study Validation of Protein ligand structures

33 Searching the PDB made simple At PDBe we ve implemented: Auto-complete suggestions Facets to narrow down search results Quality presented on search results Four views of results Moving away from entry-centricity

34 Searching PDBe

35 PDBe search bar

36 Searching PDBe

37 Searching PDBe facets provide more filtering criteria

38 Searching PDBe facets provide more filtering criteria

39 Searching PDBe sorting options

40 Entry page /4plz

41 Entry page /4plz

42 Entry page /4plz

43 Entry page /4plz

44 Entry page /4plz

45 Entry page /4plz

46 Entry page Different download options /4plz

47 Entry page Different download options /4plz

48 Entry page Visualization option /4plz

49 3D visualization Litemol viewer, interactive web-based visualization /4plz

50 3D visualization Litemol viewer, interactive web-based visualization /4plz

51 Features in Litemol Green and red map shows extra or missing atoms Shows 3D-SNFG representation of sugars Options to show domain annotation pfam Interpro Cath

52 Entry images Unique molecule, By annotation, By domain /4plz

53 Ligand and environment Ligplot shows environment Litemol viewer shows ligand with density

54 Ligand and environment

55 Ligand and environment

56 Ligand and environment

57 Functional annotation of ligand Cofactor Not an inherent property of ligand Entry specific Other biological information defines function

58 Searching PDB programmatically Resolution distribution R-Free distribution

59 Searching PDB programmatically Mol wt distribution of all hetcodes Mol wt distribution of hetcodes between mol. Wt

60 About WWPDB and PDBe PDBe web services Searching PDBe A case study Validation of Protein ligand structures

61 Validating protein ligand structures Error in model building Geometric outliers Density fit

62 Validating protein ligand structures Error in model building Clashes Badly built residue

63 Validating protein ligand structures Geometric outliers Ramachandra plot

64 Validating protein ligand structures Fit to density

65 Validating protein ligand structures Fit to density

66 Validating protein ligand structures How to find and get this information for an entry? From PDBe web pages From validation report By visualizing entry Programmatically

67 Validating protein ligand structures From PDBe web pages

68 Validating protein ligand structures How well does the model back-predict the data? Atoms bumping into each other Surprising bond angles Atoms not in electron density

69 Validating protein ligand structures From validation report Overall quality at a glance Red bar on top shows residue with poor fit to density

70 Validating protein ligand structures From validation report Ligand information in overall quality at a glance section Ligand with chirality error

71 Validating protein ligand structures By visualizing entry Viewing in litemol

72 Validating protein ligand structures By visualizing entry Viewing ligand in ligand and environment page It is possible to access this data also programmatically, by using PDBe api,

73 PDBe resources Tutorials and documentations in PDBe training page /training PDBe you tube channel More PDBe tutorials at EMBL-EBI train online

74 Thanks! PDBe.org