mat 272/bmse 272 mechanical force and biomolecules : lecture 1
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MAT 272/BMSE 272 Mechanical Force and Biomolecules : Lecture 1. Introduction: Why is force important for biomolecules?. 1951: Pauling predicts alpha helix 1954: Watson and Crick propose double-helix Late 50s: Perutz, Kendrew attain first protein structures from X-ray crystallography - PowerPoint PPT PresentationTRANSCRIPT
MAT 272/BMSE 272Mechanical Force and
Biomolecules:Lecture 1
Introduction:Why is force important for
biomolecules?
1951: Pauling predicts alpha helix1954: Watson and Crick propose double-helixLate 50s: Perutz, Kendrew attain first protein
structures from X-ray crystallography60s: Genetic code determined70s: Amino acid sequences shown to
uniquely determine protein function (Anfinsen)
80s: Biotechnology explodes(Molecular cloning , PCR)
90s: Genomes sequenced
A eucaryotic cell
Information must be stored in an ‘aperiodic crystal’-Schrodinger, 1944
replication
Eucaryotic genome packaging
A single-stranded RNA molecule can fold into an enzymatically active
structure (a ribozyme)
Proteins: Polypeptide chains that fold into globular structures with a wide variety of activities
Folded structuresMyoglobin : one chain of 153 monomers; 17 kDa
Proteasome: 28 chains of ~200 monomers each; 6.8 MDa total
1
2
3
4
How can you measure single molecules?
1) With electrical current through an ion channel (Neher and Sackmann, Nobel Prize 1991)
2) With a fluorescent dye
3) With manipulation That is, applying a relevant force to a biomolecule, and measuring resulting changes in length Single kinesins moving along
microtubules (Vale lab website)
From Nobel prize announcement
The common techniques
The Atomic Force
MicroscopeThe Optical
TweezerThe Magnetic
Tweezer
The actuator A cantilever A dielectric bead
A paramagnetic bead
Position detection Quad photodiode Quad
photodiode Video tracking
Force range 10-1000 pN 1-200 pN 0.1-100 pN
Advantages Bandwidth, sensitivity
Bandwidth, manipulation
Simplicity, constant force,
rotationDisadvantag
esLimited low-force
ability Complicated Low precision in position detection
Units, and the interesting range of forceForce~ Energy/Length; kBT ~ 4 pN nm
Process Energy Length Force
Stretching DNA ~kBT 50 nm 0.1 pN
Weak bonds ~kBT ~nm 4 pN
Unzipping DNA
2/3 H bonds = a few kBT
~nm 10-15 pN
Motor motion ATP ~ 20 kBT
1-10 nm 8-80 pN
Denaturing a protein
[many weak bonds] nm 10-200
pNCovalent
bonds1 eV ~ 40
kBT0.1 nm 1 nN
AFM
Optical
tweezers
Magnetic tw
eezers
Caveat:Reductionism
Certain proteins can only fold in the crowded interior of the cell; remove the crowding, and you’ve removed the physical impetus from the problem.Interior of an E. coli cell; from Goodsell,
1991, by way of Albertsgreen: ribosomes; red: proteins; blue: Rna
Anti-reductionism tracts
1) P. W. Anderson, Science (1972) “More is Different”
This is the start of an argument that eventually killed the SSC.2) C. R. Woese, Microbio. Mol. Bio. Rev. (2004) “A New Biology for a New Century”
In which the author questions the significance of nearly the entire field of molecular biology.
“If you read trendy intellectual magazines, you may have noticed that ‘reductionism’ is one of those things, like sin, that is only mentioned by people who are against it. To call oneself a reductionist will sound, in some circles, a bit like admitting to eating babies. But, just as nobody actually eats babies, so nobody is really a reductionist in any sense worth being against.”– Richard Dawkins
Practical mattersEvaluation
-Two graded problem sets (30% of grade)
-Half-lecture presentations (70%):These will be based on a recent paper from the field. You will get a list of papers to choose from. With my approval, you can use a paper not on the list.
The rough plan: I give 16 lectures, students give last 2-3, plus during final exam week (if necc.)
Prereq: Prior knowledge of stat. mech., not of bio
Note 5/28 is a UCSB holiday.
The websitehttp://www.engr.ucsb.edu/~saleh/#Teaching
I have posted, and will continually update:1. PPT slides from lectures (when used)2. pdf of lecture notes3. pdf of journal articles referenced (e.g. Woese
and Anderson articles)
Also, there are some links to online resources (e.g. textbooks, journal search engines) that could be useful for background research for your presentation
Practical Matters:The syllabus
Schedule and textbooks