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D atabanks + New tools = New insights

THE AXIOM. D atabanks + New tools = New insights. S imple A tom D epth I ndex C alculator. protein fold barcoding CATH – ADAPT…. -1. SADIC: a new tool to analyze atom depth. Digging inside objects to discover their origins. Birth of the Earth. protein folding. 2D.

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D atabanks + New tools = New insights

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  1. THE AXIOM Databanks + New tools = Newinsights SimpleAtomDepthIndexCalculator proteinfoldbarcoding CATH – ADAPT… -1

  2. SADIC: a newtooltoanalyzeatomdepth Digging inside objectstodiscovertheirorigins Birth of the Earth protein folding

  3. 2D HEWL 4lzt atom depth atomdepthcalculatedas the distancewith: the closestexternalwater* the closest dot of the water accessiblesurface* the closestsurfaceexposedatom* *Chakravarty S, Varadarajan R. Residue depth: a novelparameterfor the analysisofproteinstructure and stability. StructureFoldDes. 1999 7:723-732 *Pintar A, Carugo O, Pongor S.Atomdepthas a descriptorof the proteininterior. Biophys J. 2003 84:2553-2561.

  4. 2D Calculation of exposed volumes HEWL 4lzt Daniele Varrazzo, Andrea Bernini1, Ottavia Spiga, Arianna Ciutti, Stefano Chiellini,Vincenzo Venditti, Luisa Bracci and Neri Niccolai. Three-dimensional Computation of Atomic Depth in Complex Molecular Structures Bioinformatics 2005 21:2856-2860 atom depth 3D 2D

  5. atom depth 3D Calculation of exposed volumes Daniele Varrazzo, Andrea Bernini1, Ottavia Spiga, Arianna Ciutti, Stefano Chiellini,Vincenzo Venditti, Luisa Bracci and Neri Niccolai. Three-dimensional Computation of Atomic Depth in Complex Molecular Structures Bioinformatics 2005 21:2856-2860 HEWL 4lzt

  6. atom depth 3D Calculation of exposed volumes Depth index: Di,r= 2Vi,r/ V 0,r where Vi,ris the exposed volume of a sphere of radius r centered on atom i of the molecule and V0,ris the exposed volume of the same sphere when centered on an isolated atom the sphere radius r should have the biggest value which makes Vi = 0 for the most buried atom Daniele Varrazzo, Andrea Bernini1, Ottavia Spiga, Arianna Ciutti, Stefano Chiellini,Vincenzo Venditti, Luisa Bracci and Neri Niccolai. Three-dimensional Computation of Atomic Depth in Complex Molecular Structures Bioinformatics 2005 21:2856-2860 HEWL 4lzt

  7. atom depth 3D vs 2D Thr 47 α carbon Di,9 = 1.59 Ile 58 α carbon Di,9 = 0.13 Trp 28 α carbon Di.9 = 0.03 28 58 47 HEWL 4lzt

  8. 3D atomdepthanalysis Di from PDB ID 1UBQ http://www.sbl.unisi.it/prococoa/

  9. SBL BioinformaticsProjects • Projects SADIC correlated: • 1. folddependentaacompositionsofproteincores; • 2. towardsi-SADIC. • ---------------------------------------------------- • Projects SADIC uncorrelated: • 1. systematicanalysisof PPI

  10. Dianalysisofproteinatoms • definingstruturallayers in protein 3D structures • eachstruturallayerincludesatomswithsimilar Di’s • fast and accurate analysisofaacontentofstructurallayers

  11. Dianalysisofproteinatoms 3 VTR (chitinolyticenzyme 572 aa)

  12. 3D atomdepthanalysis Dimax Dimax Dimax N 0.19 CA 0.30 C 0.25 O 0.23 CB 0.50 CG 0.68 CD 0.91 CE 1.11 NZ 1.29 K63 N 0.10 CA 0.05 C 0.11 O 0.18 CB 0.02 CG 0.02 CD1 0.02 CD2 0.00 L43 http://www.sbl.unisi.it/prococoa/ N 0.38 CA 0.52 C 0.50 O 0.52 CB 0.76 CG 0.95 CD 1.17 OE1 1.24 OE2 1.24 E24 from PDB ID 1UBQ

  13. Dimaxanalysisofproteinresidues • definingaaoccupancy in proteinstruturallayers • eachstruturallayerincludesresidueswithsimilarDimax’s • fast and accurate analysisofaadistribution in proteinstructures

  14. Dimaxanalysisofproteinsingles quite a fewproteinsliketo stay single (at least in the crystalline state) -9 Bioinformatiha 2, Firenze 18 ottobre

  15. a database ofproteinsingles Experimental Method: X-RAY (79,770) Chain Type: Protein (74,456) Only 1 chain in asym. unit: (28,803) Oligomeric state: 1 (21,193) Number of Entities: 1 (3,517) Homologue Removal @ 95% identity (2,410) • DOOPS: • 2,410 proteins in the dataset • 4,657,574 atoms • 589,383 residues

  16. a database ofproteinsingles • Swiss-Prot: 540,958 proteins in the dataset (192 Maa) • DOOPS: • 2,410 proteins in the dataset • 4,657,574 atoms • 589,383 residues 0 2000 1000

  17. Dimaxanalysisofproteincores • 2,410 proteins; 4,657,574 atoms; 589,383 residues • DOOPS: • calculationof % amino acid content in L0 • the first quantitative analysisof a largearrayofproteincores! coreaaifDimax< 0.2 • ~20 % of total molecular volume ΣDOOPS aa(L0) = 106,088 (from 2410 proteins)

  18. : • Dianalysisofproteincores • foldingcluesfromaacorecomposition?

  19. : • Dianalysisofproteincores • foldingcluesfromaacorecomposition? DOOPS + CATH selectedArchitectures with ≥ 10 PDB files # ( ) domain

  20. Towardsproteinfoldingbarcodes aa % averagevalue (av) av + σ av + 2σ av - σ av - 2σ Diof 173,536 CATH domains 28 h, 5’ (average comp. time 1.72 s/domain) Calculationsperformed on 6 cores 990X CPU based computer Cys Leu Phe Val Ala CATH-ADAPT CATH - atomdepthassistedproteintomography fourlayer sandwich alpha horseshoe ribbon trefoil PDB ID 2IMH(A01) PDB ID 3CKC(A02) PDB ID 1UZK(A01) PDB ID 1RG8(A00)

  21. Towardsproteinfoldingbarcodes Puttingthe proteinuniverse in order

  22. Towardsproteinfoldingbarcodes Puttingthe proteinuniverse in order

  23. towardsi-SADIC (implemented SADIC)

  24. towardsi-SADIC (implemented SADIC) H/D exchange rate profiles

  25. towardsi-SADIC (implemented SADIC) H/D exchange rate profiles D D D D D D D D D D D D D D

  26. towardsi-SADIC (implemented SADIC) H/D exchange rate profiles

  27. towardsi-SADIC (implemented SADIC) H/D exchange rate profiles

  28. towardsi-SADIC (implemented SADIC) H/D exchange rate profiles

  29. H/D exchange rate profiles 2D atomdepthor 3D atomdepth dnwi= or atomdistancewith the nearest water molecule Di,9 = or atomdepthindexwith a probe od radius 9 Å data from Pedersen TG, Thomsen NK, Andersen KV, Madsen JC, Poulsen FM. Determination of the rate constants k1 and k2 of the Linderstrom-Lang model for protein amide hydrogen exchange. A study of the individual amides in hen egg-white lysozyme. J Mol Biol. 1993 230(2):651-660.

  30. H/D exchange rate profiles iSADICatomdepth 3D atomdepth Di,9 = or atomdepthindexwith a probe od radius 9 Å iDi,9 = aDi,9 + bASAi cDi,9 + dDnwi data from Pedersen TG, Thomsen NK, Andersen KV, Madsen JC, Poulsen FM. Determination of the rate constants k1 and k2 of the Linderstrom-Lang model for protein amide hydrogen exchange. A study of the individual amides in hen egg-white lysozyme. J Mol Biol. 1993 230(2):651-660.

  31. H/D exchange rate profiles iSADICatomdepth3D atomdepth iDi,9 = aDi,9 + bASAi cDi,9 + dDnwi

  32. protein-protein interface analysis biological vs crystallographicinterfaces

  33. crystallographicdimers biologicaldimers

  34. N ARG CA ARG C ARG O ARG CB ARG CG ARG CD ARG NE ARG CZ ARG NH1 ARG NH2 ARG H ARG HA ARG HB2 ARG HB3 ARG HG2 ARG HG3 ARG HD2 ARG HD3 ARG HE ARG HH11 ARG HH12 ARG HH21 ARG HH22 ARG N LYS CA LYS C LYS O LYS CB LYS CG LYS CD LYS CE LYS NZ LYS H LYS HA LYS HB2 LYS HB3 LYS HG2 LYS HG3 LYS HD2 LYS HD3 LYS HE2 LYS HE3 LYS HZ1 LYS HZ2 LYS HZ3 LYS vs

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