BIOLOGICAL STRUCTURE I (BIOCHEMISTRY 585)Semester: Spring, 2008Meetings: BSW 208: M 2:00-2:50pm; BSW 219: T, Th 2:00-3:15pm. NOTE TWO ROOMS!Units: 4. 2-4 hrs of lecture per week plus 0-2 hours of computer lab.Texts: Structural Biology: Practical NMR Applications, by Quincy Teng (Springer).Outline of Crystallography for Biologists, by David Blow (Oxford).In addition, original scientific articles, reviews and handouts will often be used toillustrate points. Some texts will be recommended as supplementary or backgroundmaterial.Instructors: Matt Cordes, BSW 436, [email protected] Montfort, BSW 533, [email protected]. NoneOffice Hrs: immediately after class or by appointment. Materials relevant to course but notdownloadable from website, such as class handouts, will be made available for temporarycheckout and copying.Website: http://www.biochem.arizona.edu/classes/bioc585/Questions: You are strongly encouraged to ask questions at any time during lecture, and theinstructor will stay to answer questions after lecture as long as students wish. Also, feelfree to use email to ask questions of the instructors, who will do their best to answerpromptly.Exams: The mid-term exam will be take-home and will consist of the following: questions andproblems based on the content of lectures and assigned reading; a critical review of oneor several publications related to the content of the course; problems based on theviewing of molecular structures or on analysis of data. The first exam will handed out atabout the time of Spring Break. The final exam will be written in class during thescheduled hours for the examination: Tuesday, May 13, 2-4 pm.Problem Sets: May be handed out periodically for work at home.Grading: Problem sets are 33% of the grade, and the mid-term and final count 33% each.Background: We assume that students have completed undergraduate courses in mathematics throughintegral calculus, physical chemistry, organic chemistry, and general biochemistry. Werecommend that students without background in physical chemistry not take this course.We also assume a general understanding of protein structure at the level taught in BIOC565 (Proteins and Enzymes).Computing: The student will be expected to become familiar with the use of some software programs.Students will also be given problems that involve visiting and using websites relevant tobiological structure. For these purposes, each student will have a user account for thebiochemistry computer lab in BSW 243. Students are welcome to use their own personalcomputers for this work as well, but if problems arise which are specific to their ownsetup, the course instructor may not be able (or willing) to help fix them.GENERAL DESCRIPTION OF COURSE:What this course is not:• A basic introduction to biological structure. We will not spend any time, for instance, on the basics ofprotein structure/folding. Most of this material is covered in Biochem 462 (Biochemistry) or Biochem 565(Proteins and Enzymes) and not much class time will be devoted to it here. As background material, Isuggest two texts:Introduction to Protein Architecture, by A.M. LeskIntroduction to Protein Structure, by Branden and Tooze• An exhaustive theoretical treatment of major methods for structural investigation, such as X-raycrystallography or NMR. An entire course could be taught on either one of these subjects alone.• A course covering every topic and method used in biological structure—the field is too broad and variedto do this. For instance, very little time will be devoted to low-resolution methods for structuralinvestigation.What this course is:• A graduate level course in selected modern experimental methods as applied to the investigation ofbiological structure. The goal is that the student will be equipped to recognize, comprehend and evaluatemajor techniques used in modern structural biology journal articles. Accordingly, the course is largelydevoted to the two most common techniques for high-resolution macromolecular structure determination,NMR and X-ray crystallography. These techniques will be discussed primarily as they apply to soluble,globular proteins. However, some attention will also be paid to membrane protein and nucleic acidstructure.• An exploration of issues and topics of current interest in biological structure, as taught throughspecific examples.The subject matter may be quantitative, requiring that the student be comfortable with mathematicaldescriptions. Emphasis will be placed on the physical picture behind the math, which should be accessibleto students. We recognize that students differ in their level of familiarity with physical chemistry and theassociated mathematics. We do not expect every student can understand all that is taught.OVERVIEW OF COURSE SECTIONS AND TOPICSPart I. Biomolecular NMR Spectroscopy (7.5 weeks)Matt CordesThe objectives of this section are 1) to obtain a basic understanding of how NMR works as applied tobiological molecules 2) to be able to critically evaluate original research articles that incorporate NMRtechniques 3) to gain hands-on experience in examining and analyzing NMR spectra and NMR-generatedstructures. We will use Structural Biology: Practical NMR Applications, by Quincy Teng as a primary text,though we will not rely too heavily on it or cover it in any comprehensive way. The student may also findthe following texts useful as supplementary material: Modern NMR Techniques for Chemistry Research, byAndrew Derome (Pergamon Press), NMR of Proteins and Nucleic Acids, by Kurt Wuthrich (WileyInterscience), Biomolecular NMR Spectroscopy by Jeremy N.S. Evans (Oxford) and Protein NMRSpectroscopy, by Cavanagh et al. (Academic Press). Readings will also include many handouts andoriginal research/review articles from the literature. In particular, we will critically examine severalresearch articles dealing with NMR studies of the protein calmodulin, as an exemplary illustration of theutility of NMR in probing protein structure and dynamics. Discussion of calmodulin will continue in Dr.Montfort's X-ray crystallography portion, allowing us to compare and contrast the strengths and limitationsof the two techniques. Approximately 3 hours of class time per week will be lectures. Approximately 1hour a week will be spent in the computer lab analyzing NMR data and examining structures generatedfrom NMR data. To facilitate these analyses, we will become familiar with NMR data analysis