Integrative modeling from single proteins to assemblies

1. Integrative modeling from single proteins to assemblies • Daniel Russel • Šali Lab, UCSF, Google • August, 2012

2. TRiC/CCC Sali, Frydman, Chiu Actin Sali, Chiu RyR channel Sali, Serysheva, Chiu Ribosomes, Sali, Frank; Sali, Akey Hsp90 landscape Sali, Agard Nuclear Pore Complex, Sali, Rout, Chait Nup84 complex, Sali, Rout, Chait Nuclear Pore Complex transport, Sali, Rout, Chait, Chook, Liphardt Microtubule nucleation Sali, Agard 26 Proteasome Sali, Baumeister PCS9K-Fab complex Sali, Cheng, Agard, Pons Spindle Pole Body Sali, Davis, Muller Chromatin globin domain Marti-Renom Lymphoblastoid cell genome Alber, Chen Assembly Modeling

3. Why we need data integration? 100Å 1Å assembly residues domains proteins atoms Protein structure prediction X-ray Crystallography Cryo-electron microscopy Phylogenetic profiling Gene/protein microarrays Ab initio Modeling NMR spectroscopy Cryo-electron tomography Hydrodynamics Experiments SAXS Immuno- Precipitation/MS Immuno-electron microscopy Yeast-two hybrid Chemical Cross-linking Computational Docking Bioinformatics Information retrieval Quantitativeimmunoblotting Site-directed mutagenesis FRET [D. Russel, K. Lasker, B. Webb, J. Velazquez-Muriel, E. Tjioe, D. Schneidman-Duhovny, B. Peterson, A. Sali. Putting the pieces together: integrative structure determination of macromolecular assemblies. PLoS Biol 2012]

4. Integrative structure modeling

5. Integrative structure modeling

6. IMP C++/Python library multifit/restrainer Chimera tools/ web apps Domain-specific applications IMP Simplicity Expressiveness http://www.integrativemodeling.org Russel et al, PLoS Biology, 2012

7. Connecting data and algorithms 2D EM Monte Carlo SAXS Rigid atomic models Molecular dynamics Proteomics Flexible homology models DOMINO Yeast two hybrid Brownian dynamics 3D EM Coarse grained structures PDB IMP base RMF

8. File formats Protein structure prediction X-ray Crystallography Cryo-electron microscopy Phylogenetic profiling Gene/protein microarrays Ab initio Modeling NMR spectroscopy Cryo-electron tomography Hydrodynamics Experiments SAXS Immuno- Precipitation/MS Immuno-electron microscopy Yeast-two hybrid Chemical Cross-linking Computational Docking Bioinformatics Information retrieval Quantitativeimmunoblotting Site-directed mutagenesis

9. Rich visualization

10. Modeling transport varying concentrations variable numbers of binding sites physical properties of fg chains varying interaction strengths with Barak Raveh

11. Dynamics models

12. Reproducible modeling Gatheringexperimental data and other information Designing modelrepresentationand evaluation Samplinggood models Analyzing modelsand information

13. Reproducible modeling Gatheringexperimental data and other information Designing modelrepresentationand evaluation The paper: experimental data experimental protocol pictures of structures analysis of structure sketch of modeling protocol Samplinggood models Analyzing modelsand information

14. Reproducible modeling Gatheringexperimental data and other information Designing modelrepresentationand evaluation Samplinggood models The trash:all the needed details to practically reproduce the computational result Analyzing modelsand information

15. Acknowledgments