Biochemistry 766: Nucleic Acids

http://www.biosci.ohio-state.edu/~mfoster/biochem766/

http://carmen.osu.edu

Winter Quarter 2009, 3 cr., MWF 10:30-11:20, BI 668

Instructors:            Mark Foster, 734 Riffe, 292-1377, foster.281@osu.edu

Karin Musier-Forsyth, 3033B McPherson or 909 BioSci; 292-2021, musier-forsyth.1@osu.edu

Office hours: Wednesdays, 11:30-12:30 pm

TA:                           Yiren Xu, Xu.172@osu.edu; 688-8146; Office Hours: TBA, 732 Riffe

Primary Text:

Nucleic Acids in Chemistry and Biology. Blackburn, Gait, Loakes and Williams, eds. Royal Society of Chemistry, 2006, 3rd edition. ISBN: 978-0-85404-654-6.

Grading:

Problem Sets: 20%, Paper reviews: 10%, Oral Presentations: 10%, Midterm: 30%, Final: 30%

Lecture Topics

Introduction

Nucleic acids biochemistry; history and context

Nucleic acid nomenclature; tautomerism; ionization

Structure

Base pairing, helical structure, ion binding, hydration

Computer-aided structure analysis (RASMOL/PYMOL; BPL computing lab)

Chemical and Biochemical Methods

Synthesis

Reactivity

Sequencing, identification of modified nucleosides

DNA/RNA structure analysis by chemical/enzymatic probing and phylogenetic data

Nucleoside analogs, phophorothioates, NAIM

SELEX

RNA Interference

Physical Methods

Nucleic acid crystallography

NMR of Nucleic Acids

Spectroscopy of nucleic acids

Conformational changes

Single molecule methods

Interactions

Ligand binding in the major and minor grooves, intercalation, drug design

Protein-DNA interactions; motifs, major and minor groove recognition, bending

RNA-protein interactions

Protein enzymes

RNA catalysis

Ribozymes

The ribosome

Oral Presentations/Literature Discussions

Final Exam: Thursday, March 19, 9:30-11:18 am; location TBA

Class Materials

Materials for the course will include assigned text readings, handouts provided in class, and materials available on-line via Carmen ( http://carmen.osu.edu ). Other sources of information include the current research literature as well as literature and structural databases.

Computer-Aided Structure Analysis

We will be making use of molecular visualization software to learn about nucleic acids structure and interactions. You will be encouraged to learn to use the Pymol visualization program, although similar alternative programs may be also used. Pymol is available in the computing lab on the second floor of the BPL, versions are freely available and can be installed on your own (or laboratory) computer. A tutorial on the use of the software will be provided in one class session.

Oral Presentations & Written Paper Reviews

Students will be required to read, discuss and present essential aspects of selected research papers orally and in writing. During the last week, students will make oral presentations on a selected paper topic; one evening session may be scheduled to complement the in-class sessions.

Other texts (on reserve in BPL)

Nucleic Acids: Structure, Properties and Functions. Bloomfield, Crothers & Tinoco. University Science Books, 2000, ISBN 0-935702-49-0

Principles of Nucleic Acid Structure. Saenger, Springer Verlag, New York, 1984

Bioorganic Chemistry: Nucleic Acids. Hecht, Oxford University Press, 1996

Molecular Biology. Weaver, McGraw-Hill, 3rd ed., 2005

Computer and web resources

Data

 

Protein Data Bank (PDB)

http://www.rcsb.org/pdb

Nucleic Acid Database

http://ndbserver.rutgers.edu:80

BMRB

http://www.bmrb.wisc.edu

Software

 

PyMOL

http://pymol.sourceforge.net

RASMOL

http://www.umass.edu/microbio/rasmol

MOLMOL

http://www.mol.biol.ethz.ch/wuthrich/software/molmol

Chimera (UCSF)

http://www.cgl.ucsf.edu/chimera/

VMD (UIUC)

http://www.ks.uiuc.edu/Research/vmd/

Mfold

http://www.bioinfo.rpi.edu/applications/mfold/old/rna/form3.cgi

(PDB repository)

http://www.rcsb.org/pdb/software-list.html

Literature

 

Entrez/PubMed

http://www3.ncbi.nlm.nih.gov/Entrez

Ohio-Link Journal Center

http://journals.ohiolink.edu/cgi-bin/sciserv.pl?collection=journals

OSCAR databases

http://www.lib.ohio-state.edu/find/subject.php

Journals (by no means a comprehensive list)

Biochemistry

http://pubs.acs.org/journals/bichaw/index.html

Cell

http://www.cell.com

Curr Opin Struct Biol

http://www.current-opinion.com/jstb/about.htm?jcode=jstb (OhioLink)

EMBO J

http://www.emboj.org

J Mol Biol

http://www.academicpress.com/jmb (OhioLink)

Nature

http://www.nature.com

Nature Struct Biol

http://www.nature.com/nsmb/

Nucleic Acids Res

http://www.oup.co.uk/nar/contents

Proc Natl Acad Sci USA

http://www.pnas.org

RNA

http://www.rnajournal.org/

Science

http://www.sciencemag.org/

Biochemistry 766 Preliminary lecture schedule:

Week

Day

Date

Topic

Instructor

Reading

Assignment

1

Mon

1/5

Intro/Nomenclature

Mark

Ch. 1, 2.1; Watson & Crick Nature 1953

 

 

Wed

1/7

Structure, part 1

Karin

2.1.2, 2.2

Read Moran & Kool PNAS 1997

 

Fri

1/9

Structure, part 2

Karin

2.3, 2.4

PS #1 available (Karin)

2

Mon

1/12

Physical Properties: Thermodynamics Computer-aided structure analysis

Karin

2.1.3, 2.4.4.1, 2.5

 

 

Wed

1/14

(PyMOL; BPL computing lab)

Mark

 

 

 

Fri

1/16

Higher order structure; RNA/DNA folding

Karin

2.6, 7.1

PS #1 due; PS #2 available (Mark)

3

Mon

1/19

MLK Day, no class

 

 

 

 

Tue

1/20

OSBP Seminar, 4 PM, 170 H&L, Lynne Maquat

 

Wed

1/21

DNA, RNA sequencing, modified nucleosides

Mark

5.1-5.3, 7.2, 11.6

PS #2 due; PS #3 available (Mark)

 

Fri

1/23

Phylogenetic co-variation; SELEX

Mark

Massire 1998 JMB; Hermann & Patel 2000

 

4

Mon

1/26

Chemical and enzymatic probes

Mark

Zarrinkar & Williamson 2004

Correll et al. 1997

 

 

Wed

1/28

Nucleoside analogs, phosphorothioates

Mark

4.3-4.4, NAIM Review

PS #3 due

 

Fri

1/30

NAIM

Mark

 

 

5

Mon

2/2

X-ray crystallography

Mark

11.3

 

 

Wed

2/4

X-ray cont. NMR Spectroscopy

Mark

11.2

 

 

Thu

2/5

Exam I (evening)

 

 

 

 

Fri

2/6

NMR Spectroscopy

Mark

11.2

Paper selections for oral presentations approved by today

6

Mon

2/9

Optical Spectroscopy, FRET

Karin

11.1

Assign papers to review

 

Wed

2/11

RNA interference/ micro RNAs

Karin

5.7.2

 

 

Fri

2/13

Catalytic RNAs

Karin

7.6.2

 

7

Mon

2/16

Catalytic RNAs

Karin

 

Paper review discussion

 

Wed

2/18

Catalytic RNAs

Karin

 

Written reviews due. Assign PS#4 (Karin)

 

Fri

2/20

Protein-DNA interactions

Karin

10.1-10.4

 

8

Mon

2/23

Protein-DNA interactions

Karin

10.5-10.8

 

 

Tue

2/24

OSBP Seminar, 4 PM, 170 H&L Jamie Williamson

 

Wed

2/25

Protein-RNA interactions

Karin

10.9

 

 

Fri

2/27

Protein-RNA interactions

Karin

 

PS #4 due

9

Mon

3/2

Single Molecule Methods

Mark

11.5, Bustamante 2003; Ha 1999

 

 

Wed

3/4

Ligand binding in major/minor groove, intercalation, drug design

Mark

9

 

 

Fri

3/6

Ribosome

Mark

 

 

10

Mon

3/9

Paper presentations (+ one evening)

 

 

 

 

Wed

3/11

Paper presentations

 

 

 

 

Fri

3/13

Paper presentations

 

 

 

Final

Thu

3/19

Final Exam (9:30-11:18)