Instructor:                     Dr. Satish Nair (office hours by appointment)
Teaching Assistant:   Qian Bian and Ionel (Jon) Rata
Meetings:                      Tuesday & Thursday 12:45 AM – 2 PM
                                         Room A446 in CLSL
Suggested texts:        “Crystallography Made Crystal Clear” by Gale Rhodes
                                         “Introduction to Protein Structure” by Branden & Tooze

Student Assignments: 

Ten problem sets (take home) will be assigned. 

You may opt to drop the lowest grade on 1 of these problem sets.

These will account for 34% of final grade

Exams:  A midterm and a final. Each will account for 33% of final grade.

Topics to be covered:
          Introduction (review) of protein structural elements
          Review of protein and nucleic acid structural motifs
          Principles of nuclear magnetic resonance spectroscopy
          Principles of X-ray crystallography (with working examples)
          Introduction to Bioinformatics

Week 1 (Jan 18 and 23):
(Mostly review) Preliminary considerations -
            Overview of Proteins
            Properties of amino acids
            Protein jargon
            The peptide bond
            Physical interactions that determine properties of proteins
            The hydrophobic effect
Problem Set 1 handed out on Jan 23 due on Jan 30.
             
Week 2 (Feb 1 and Feb 6):
(Mostly review) Higher order protein structure -
            Secondary, tertiary and quarternary structures
            Helices
            Zimm and Bragg parameters
            Coiled coils (leucine zippers)
            Beta structures
            Alpha-Beta barrel
            Membrane proteins
Problem Set 2 handed out on Feb 6 due on Feb 13.

Week 3 (Feb 8 and Feb 13):
Characterization of proteins in solution -
            Volume and surface area
Hydrodynamic properties
            Diffusion
            Dynamic light scattering
Fluorescence -
            The fluorescence process
            Instrumentation
            Multicolor labeling experiments
            FRET (The Forster equation)

Week 4 (Feb 15 and Feb 20):
Quantum mechanical properties of proteins -
            Spin
Spin packets
            Nuclear Magnetic Resonance
            Relaxation
Nuclear Magnetic Resonance spectroscopy -
            T1 and T2 processes
            Rotating frames of reference
            Pulsed magnetic fields
Problem Set 3 handed out on Feb 15 due on Feb 22.

Week 5 (Feb 22 and Feb 27):
Nuclear Magnetic Resonance spectroscopy (con’td) -
            Chemical shift
Spin-spin coupling
Time domain NMR signal
The frequency convention
Fourier transforms
            Convolution theorem
            The digital Fourier transform
            Sampling error
Problem Set 4 handed out on Feb 27 due on Mar 6

Week 6 (Mar 1 and Mar 6):
Fourier transform NMR spectroscopy -      
            90 degree FID sequence
            Spin-echo sequence
            Inversion recovery sequence
            2D NMR
Protein NMR spectroscopy -           
            Correlated spectroscopy (COSY)
            Total correlation spectroscopy (TOCSY)
            Decoupling

Week 7 (Mar 8 and Mar 13):
Fourier transform NMR spectroscopy (cont’d) –
            Nuclear Overhauser Effect (NOE) Spectroscopy
            Inverse NMR Experiments
            Heteronuclear single quantum correlation

Assignment of spectra –

            Homonculear sequential assignment
            Sequential contacts
            Interresidual cross signals
Problem Set 6 handed out on Mar 6 due on Mar 13.

MIDTERM EXAMINATION (in class March 15)

SPRING BREAK (March 17 – 26)

Week 8 (Mar 27 and Mar 29):
Diffraction theory –
            Vector addition of electromagnetic waves
            Scattering by 2 electrons not at origin zero
            Scattering by an atom
            Scattering by a system of atoms (unit cell)
            Scattering by a crystal
Problem Set 7 handed out on Mar 27 due on Apr 3.

Week 11 (Apr 3 and April 5):
Crystallographic symmetry-
            Graphic symbols of symmetry elements
            Point groups and space group
            Asymmetric unit
Patterson synthesis-
            The Patterson function
            Anomalous difference Patterson
            Fourier synthesis          
Problem Set 8 handed out on April 5 due on April 12.
                       
Week 12 (April 10 and April 12):

Multiple Isomorphous Replacement (MIR)

            Heavy atom refinement
            Single isomorphous replacement (SIR)
            Multiple isomorphous replacement phasing
MIR with Anomalous Scattering (MIRAS)
            The anomalous signal
            Absolute configurations
            Single Anomalous Scattering

Week 13 (April 17 and April 19):

Molecular Replacement

            Rotation functions
            Translation functions
            Noncrystallographic symmetry

Multiwavelength Anomalous Diffraction

            Choice of wavelength
            Data collection strategy
            Location of anomalous scatterers
Problem Set 9 handed out on April 17 due on April 24.

Week 14 (April 22 and April 24):

Software and validation

            Procheck/Prowat
            Eisenberg Plots
            Cross validation
            Pymol/Ribbons/Molview                      
Problem Set 10 handed out on April 24 due on May 1.

Week 15 (April 29 and May 1):

Bioinformatics

            The BLAST search
            Protein secondary structure prediction
            Homologous structure alignment
            The Protein Data Bank
            Proteomics      

Week 16 (May 3): Review for Final Exam

FINAL EXAM: MONDAY MAY 10 at 1:30 PM (Tentative).