Text: No required text book. Handouts will be given during the classes. Suggested references:

Transcription

1 Text: No required text book. Handouts will be given during the classes. Suggested references:

2 COURSE CONTENTS: Biological web resources, structure databases, structure alignment, protein, DNA, and RNA structure, molecular recognition, threading methods for protein structure modeling, protein dynamics, structural analysis and molecular simulation algorithms. GRADE: Course grade will be based on eight homework projects, a mid-term examination and a final examination as follows: Percent of final grade: Homework Projects: 30 % Mid-term Examination: 35 % Final Examination: 35 % The final and mid-term examinations will be comprehensive written tests. Eight homework projects will be assigned by the instructors. You should hand in your projects by the due date specified by the instructors. Points will be subtracted for projects submitted after the due date. Statement for Students with Disabilities Any student requesting academic accommodations based on a disability is required to register with Disability Services and Programs (DSP) each semester. A letter of verification for approved accommodations can be obtained from DSP. Please be sure the letter is delivered to me (or to TA) as early in the semester as possible. DSP is located in STU 301 and is open 8:30 a.m. 5:00 p.m., Monday through Friday. The phone number for DSP is (213) Statement on Academic Integrity USC seeks to maintain an optimal learning environment. General principles of academic honesty include the concept of respect for the intellectual property of others, the expectation that individual work will be submitted unless otherwise allowed by an instructor, and the obligations both to protect one s own academic work from misuse by others as well as to avoid using another s work as one s own. All students are expected to understand and abide by these principles. SCampus, the Student Guidebook, contains the Student Conduct Code in Section 11.00, while the recommended sanctions are located in Appendix A: Students will be referred to the Office of Student Judicial Affairs and Community Standards for further review, should there be any suspicion of academic dishonesty. The Review process can be found at:

3 Tentative Schedule: Lecture (1) Principles of Protein Structure Lecture (2) X-ray Crystallography and NMR Spectroscopy Lecture (3) Structure-Based Databases Data Formats Lecture (4) Interactive Molecular Graphics and Analysis Tools Lecture (5) Structure and Sequence Alignment Methods Lecture (6) Protein Classifications and Functional Annotation Lecture (7) Comparative Protein Structure Modeling Lecture (8) Model Building and Structure Assessment Lecture (9) Protein Interaction Networks Lecture (10) Principles of Protein Interactions Lecture (11) Protein Docking Methods Lecture (12) Structure Determination of Large Complexes: Cryo-electron Microscopy Lecture (13) Structure Characterization by Fitting of Atomic Structures into Cryo-EM Density Maps Lecture (14) Molecular Organization of the Cell Lecture (15) Cryo-electron Tomography and visual proteomics Lecture (16) Reaction-Diffusion Modeling of Biological Processes in Crowded Cellular Environments Lecture (17) Higher-order Structural Organization of Genomes Lecture (18) Principles of Nucleic Acid Structure Lecture (19) Discovery of the Double Helix Lecture (20) Sequence-dependence of DNA Structure and its Analysis and Prediction

4 Lecture (21) Protein-DNA Recognition Lecture (22) Electrostatics in Molecular Interactions and Solvation Models Lecture (23) Specific Protein-DNA Binding: Transcription Factors Lecture (24) Cooperativity in Protein-DNA Recognition: Co-factors, Oligomerization, and the Enhanceosome Lecture (25) Non-Specific Protein-DNA Binding: The Nucleosome Lecture (26) Model Building and Molecular Simulations of Protein-DNA Interactions Lecture (27) RNA Structure: Secondary Structure Prediction and RNA Folding Lecture (28) Protein-RNA and RNA-RNA Binding Lecture (29) Molecular Machinery of the Ribosome Lecture (30) Cell-Cell Adhesion Reading Assignments Lecture (1) C. Branden and J. Tooze. Introduction to Protein Structure. Second Edition Chapters 1 and 2. Pages Lecture (2) W. Hendrickson. X-rays in molecular biophysics. Physics Today Pages K. Wuethrich. Protein structure determination in solution by Nuclear Magnetic Resonance spectroscopy. Science Vol Pages Lecture (3) Structural Bioinformatics. Vol. 44. Chapter 8. The PDB and other data formats. Chapter 9. The Protein Data Bank. Lecture (4) Structural Bioinformatics. Vol. 44. Chapter 7. Molecular Visualization. Lecture (5) Structural Bioinformatics. Vol. 44. Chapter 16. Structure Comparison and Alignments. Ortiz, A. R.; Strauss, C. E. M.; Olmea, O., MAMMOTH (Matching molecular models obtained from theory): An automated method for model comparison. Protein Sci. 2002, 11,

5 Holm, L.; Sander, C., Alignment of three-dimensional protein structures: network server for database searching. Methods Enzymol 1996, 266, Lecture (6) Structural Bioinformatics, Vol. 44; Chapter 26. Fold Recognition Methods. K. Karplus et al. Hidden Markov models for detecting remote protein homologies. Bioinformatics Vol. 14. Pages D.T. Jones et al. A new approach to protein fold recognition. Nature Vol Pages Lecture (7) Structural Bioinformatics. Vol. 44. Chapter 25. Homology Modeling. A. Sali and T.L. Blundell. Comparative Protein Modelling by Satisfaction of Spatial Restraints. J. Mol. Biol Vol Pages Lecture (8) D. Eramian et al. How well can the accuracy of comparative protein structure models be predicted? Protein Science Vol. 17. Pages M. Shen and A. Sali. Statistical potential for assessment and prediction of protein structures. Protein Sci Vol. 15. Pages Lecture (7) B.A. Shoemaker and A.R. Panchenko. Deciphering protein-protein interactions. Part I. Experimental techniques and databases. PLoS Comput. Biol Vol. 3. e42. Pages B.A. Shoemaker, A.R. Panchenko. Deciphering protein-protein interactions. Part II. Computational methods to predict protein and domain interaction partners. Vol. 3. e43. Pages Lecture (8) O. Keskin et al. Principles of protein-protein interactions: what are the preferred ways for proteins to interact? Chem. Rev Vol Pages Lecture (11) F. Alber et al. Integrating diverse data for structure determination of macromolecular assemblies. Annu. Rev. Biochem Vol 77. Pages Lecture (12) M. Beck et al. Exploring the spatial and temporal organization of a cell s proteome, J. Struct. Biol In press. Gavin E. Murphy and Grant J. Jensen (2007) Electron Cryotomography BioTechniques, vol A. Leis et al. Visualizing cells at the nanoscale. Trends Biochem. Sci Vol. 34. Pages Lecture (13)

6 F. Alber et al. Integrating diverse data for structure determination of macromolecular assemblies. Annu. Rev. Biochem Vol 77. Pages M. Beck et al. Exploring the spatial and temporal organization of a cell s proteome, J. Struct. Biol In press. Lecture (14) Z. Li and G.J. Jensen. Electron cryotomography: a new view into microbial ultrastructure. Curr. Opin. Microbiol Vol. 12. Pages Lecture (15) M. Beck et al. Visual proteomics of the human pathogen Leptospira interrogans. Nature Methods Vol. 6. Pages M. Beck et al. Exploring the spatial and temporal organization of a cell s proteome, J. Struct. Biol In press. Lecture (16) A. Elcock. Models of macromolecular crowding effects and the need for quantitative comparisons with experiment. Curr. Opin..Struct. Biol Vol. 20. Pages Lecture (17) T. Misteli. Beyond the Sequence: Cellular Organization of Genome Function. Cell Vol. 128, Pages Lecture (18) W. Saenger. Principles of Nucleic Acid Structure. First edition Selected chapters. Proteopedia Lecture (19) E. Chargaff. The separation and quantitative estimation of purines and pyrimidines in minute amounts. J. Biol. Chem Vol Pages L. Pauling and R.B. Corey. A proposed structure for the nucleic acids. Proc. Natl. Acad. Sci. USA Vol. 39. Pages J. Watson and F. Crick. Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid. Nature Vol Pages Recommended: B. Maddox. Rosalind Franklin - The Dark Lady of DNA. Lecture (20) A.A. Gorin et al. B-DNA twisting correlates with base-pair morphology. J. Mol. Biol. 1995, 247: Handout. Helical parameters translations and rotations. R. Rohs et al. Structural and energetic origins of sequence-specific DNA bending: Monte Carlo simulations of papillomavirus E2-DNA binding sites. Structure Vol. 13. Pages Lecture (21) C.W. Garvie and C. Wolberger. Recognition of specific DNA sequences. Mol Cell

7 2001. Vol. 8. Pages R. Rohs et al. Origins of specificity in protein-dna recognition. Annu. Rev. Biochem. 2010, 79: Lecture (22) B. Honig and A. Nicholls. Classical electrostatics in biology and chemistry. Science Vol Pages Lecture (23) R. Joshi et al. Functional specificity of a Hox protein mediated by the recognition of minor groove structure. Cell Vol Pages Lecture (24) M. Kitayner et al. Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs. Nat. Struct. Mol. Biol Vol. 17. Pages D. Panne. The enhanceosome. Curr. Opin. Struct. Biol Vol. 18. Pages Lecture (25) C.A. Davey et al. Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution. J. Mol. Biol Vol Pages R. Rohs et al. The role of DNA shape in protein-dna recognition. Nature Vol Pages Lecture (26) R. Rohs et al. Nuance in the double-helix and its role in protein-dna recognition. Curr. Opin. Struct. Biol Vol. 19. Pages D. Vuzman et al. Searching DNA via a Monkey Bar Mechanism: The Significance of Disordered Tails. J. Mol. Biol Vol Pages Lecture (27) N.B. Leontis et al. The building blocks and motifs of RNA architecture. Curr. Opin. Struct. Biol Vol.16. Pages P. Schuster et al. RNA structures and folding: from conventional to new issues in structure predictions. Curr. Opin. Struct. Biol Vol. 7. Pages Lecture (28) T. Hermann and E. Westhof. Non-Watson-Crick base pairs in RNA-protein recognition. Chem. Biol Vol. 6. Pages E. Westhof and D.J. Patel. Nucleic acids. From self-assembly to induced-fit recognition. Curr. Opin. Struct. Biol Vol. 7. Pages Lecture (29) T.M. Schmeing and V. Ramakrishnan. What recent ribosome structures have revealed about the mechanism of translation. Nature Vol Pages

8 A. Yonath. Polar Bears, Antibiotics, and the Evolving Ribosome. Angew. Chem. Int. Ed. Engl Vol. 49. Pages Lecture (30) L. Shapiro et al. Structural basis of cell-cell adhesion by cadherins. Nature Vol Pages Patel et al. Cadherin-mediated cell-cell adhesion: sticking together as a family. Curr. Opin. Struct. Biol Vol. 13. Pages