This is a series of 15-lecture, 1-credit modules.  These modules introduce students to different techniques commonly used in mechanistic and structural biology.  All modules are independent but require Biochemistry/Biophysics  144-147 or permission of the instructor as prerequisites.  Dr. Barry Lentz serves as the Coordinator of this series, although each module has its own course director.  In some cases, course-meeting times can be adjusted to meet the needs of students; contact the course director to inquire.
 

Biochemistry 150: Imaging of macromolecular assemblages [Costello, Erie, Jacobson, Salmon, Superfine; 1/13/00-3/31/00; Offered in spring semester of even years; lectures TTh2-3:15, laboratory demonstrations F2-4].  Cross listed with Biology 175.

For Biophysics students, this course is divided into two sections.  Both lectures and lab demonstrations are required for each section.  A detailed syllabus is available on the Biophysics web page (http://hekto.med.unc.edu:8080/).

Biochemistry 150a: Introduction to light microscopy  [Salmon (Course Director, 2-2265, tsalmon@email.unc.edu); 1/13/00-2/11/00; 1 credit hour.]

This section introduces the fundamentals of light microscope design.  The Biophysics student well versed in optics might find this portion repetitive of earlier courses.

Biochemistry 150b: Advanced Topics in Imaging [Costello? (course director; 966-6981, mjc@med.unc.edu), Erie?, Jacobson¶, Salmon*, Superfine#; 2/14/00-3/31/00; 2 credit hours.]

In this section, Drs. Salmon and Jacobson provide a treatment of optical imaging, including fluorescence and confocal techniques.  Dr. Costello leads a discussion of electron imaging, including transmission electron microscopy (TEM), scanning electron microscopy (SEM), and image interpretation.  Finally, Drs. Superfine and Erie present a brief description of the basic principles and applications of mechanical imaging using scan-ning probe microscopy (SPM).
 

Biochemistry 151: Macromolecular interactions [Currently not offered; Time TBA]

a.    Surface Plasmon Resonance (SPR)
         i.      basic principles of SPR
         ii.     kinetics of macromolecular interactions measured by SPR
         iii.    analysis of macromolecular binding equilibria

b.    Analytical Ultracentrifugation
         i.       introduction to analytical ultracentrifugation
         ii.      sedimentation velocity to detect macromolecular complexes
         iii.     sedimentation equilibrium and macromolecular size
         iv.     macromolecular shape

c.     Biological MicroCalorimetry

         i.     basic principles in calorimetry
         ii.    titration microcalorimetry to monitor macromolecular binding
         iii.   differential scanning calorimetry and macromolecular domain structure
 

Biochemistry 152: Macromolecular NMR: structure & dynamics [Campbell; 966-7139, campbes1@hasty; 2/18/00-3/29/00; Time TBA]

• Basic principles of macromolecular NMR spectroscopy
• NMR multi-pulse experiments
COSY/TOCSY, NOESY, heteronuclear correlation
• The NMR assignment problem in biopolymers
Multidimensional homonuclear and heteronuclear approaches
• Three dimensional protein structures by NMR
principles of protein backbone analysis, NMR input for biopolymer structure determination, model building using interactive computational methods
• Dynamics by NMR
hydrogen bonds and amide-proton exchange, kinetic studies using NMR
biopolymer dynamics
• NMR studies of biopolymer-ligand interactions
 

• Growing and characterizing crystals of macromolecules
crystal symmetry, system and space group determination
• Nature of X-rays; principles of diffraction, and diffaction of a single crystal of a macromolecule
• Methods to phase a macromolecular structure
Patterson, multiple isomorphous replacement, molecular replacement
• Interpreting electron density in terms of protein structure
• Refinement of a raw macromolecular structure
 

• Introduction to simulations: Formulation of a detailed model of molecular systems and its relation to physical observations
• Macromolecular force fields: Form and parameters; PBC and long-range forces
• Water: the SPC model and its interpretation (TIP3P, SPCE)
• Dynamics algorithms: integration methods; ensembles: temperature, pressure.
• Intramolecular motion: Diffusion and oscillation; use of correlation functions
• Intramolecular motion: Complete sampling of Boltzmann distributions including transition intermediates, the multiple-minima problem, searching conformation space
• Structure refinement: Simulated annealing
• Free energy from simulations: Potentials of mean force and molecular transformation,
• integration methods (slow growth/TI, FEP, umbrella sampling), thermodynamic cycles.
• Water: Water models (SPC, TIP3P, SPCE) and analysis of water structure
• Application to molecular interactions: HIV protease inhibitor
• Simplified force-fields and heuristic methods; the protein folding problem

Biochemistry 155: Electrical signals from macromolecular assemblages [Cross-listed as the first section of Neurobiology 222; R. Cheney, R. Rosenberg, G. Oxford (coordinator; 962-7157, gsox@med.unc.edu), B. Pallotta, A. Stuart; 8/18/99-9/27/99, NOTE FALL SEMESTER; 10-11:50, 74 MSRB, MWF; 2 credits]

 a. Introduction to information theory

 i.     information content of biomolecular sequences
 ii     information and entropy

 i.      databases and database structure
 ii.     biomolecular databases: DNA and protein sequences, genomes, protein structures
 iii.    interfaces and data access

 i.       internet organization and architecture
 ii.      distributed computing and server-client information systems
 iii.     research and collaboration on Internet
 iv.     electronic publishing
 v.      molecular visualization

 i.       string alignment problem
 ii.      scoring functions and substitution matrices
 iii.     BLAST, FASTA, and Smith-Waterman algorithms
 iv.     multiple sequence alignment

 i.       neural networks
 ii.      genetic algorithms
 iii.     Markov models

 i.      secondary and tertiary structure prediction
 ii.     pattern recognition and identification in sequences
 iii.    genome informatics: computational gene identification and prediction
 iv.     accuracy of structure and gene prediction