Transcript Determination of the structure

Molecular Biophysics
Biomolecular Physics
I urge you to visit
different web site
- to study
manuals and
- to look at
structures
To Study Cells: many different aspects
The histones
(water
insoluble
proteins with
basic character,
isoelectric
point at pH
8.5) are in
connections
with DNA of
inactive genes
in the nucleus.
What subjects the course
Molecular Biophysics
ought to have to cover?
Opportunities in Biology for Physicists
While the number of physicists doing biology is still relatively small, it is
one of the fastest growing fields in the discipline. The American Physical
Society, the professional organization for physicists, is putting on a
conference for young scientists titled ''Opportunities in Biology for
Physicists.''
Biology is increasingly drawing in scientists from many disciplines
beyond physics, including mathematics, computer science, and
engineering.
Indeed, some of science's most vibrant areas reside at the boundaries
of the old disciplines -proof, some say, that the old ways of
conceptualizing problems are holding back progress.
''Ask not what physics can do for biology,'‘
said Hans Frauenfelder, one of the field's pioneers,
''Ask what biology can do for physics.'' .
(Adaptation of famous phrase from J.F. Kennedy)
''Biology has provided physics with its new frontier,'‘
said Robert Laughlin, who won the 1998 Nobel prize in physics
(quantum Hall effect) and now devotes himself to theoretical problems in
biology.
''The whole problem is that we are living in the 21st century with
these 19th century guilds,''
said John Hopfield, a Princeton scientist, one of the first
physicists to move into biology.
Fundamental aspects of Physics
•Systems with a large number of atoms
•Molecular crystals: Repetitive structures
•Importance of fluctuations
•Difference between forces in biomolecules and forces in solids and
liquids
•Use of quantum physics (photosynthesis)
•Complexity and hierarchy of structures
•Order-disorder phenomena. Ising model
•Dissipative processes. Origin of life
•Information storage and transfer
•Production, storage and transfer of energy
Biomolecular Physics
Determination of the structure
x-ray, NMR, EPR,
hydrodynamics, ε, χ,
computational methods
Equilibrium properties
Thermodynamics and statistical mechanics
Cooperative phenomena
Kinetic properties
Relaxation, chemical kinetics
Fluctuations
Biomolecules & Biopolymers
Constituents :H, C, N, O, P, S, Ca, Cu, Mg, Fe, Zn, Mn
Biomolecules --Atoms --Quantum Physics
SOLIDS: strong forces
LIQUIDS: weak forces
BIOMOLECULES: strong + weak forces
Determination of the structure
Geometrical distribution of atoms within molecules, crystals and liquids
Methods
•x-ray diffraction
•NMR
•Electron microscopy
The scattering of electrons and x-rays depends on interatomic distances.
•Neutron diffraction is used for H-atoms .
•Tunneling microscopy
•Computational methods
•Microwave spectroscopy gives information on vibrational levels, moment of
inertia -- atomic distances
Biomolecules → Life
The interaction between biomolecules determines the development and
evolution of living systems.
Biomolecules contain a large number of atoms (102 to 1010)
The hierarchy of living things
Organism
>1020
Cell
1010
Organelle
105–106
Biomolecule 103–104
Molecule
10 –100
Atom
1
Atom
Physics
Quantum mechanics
Molecule
Vibration-rotations, Chirality,
Radiationless transitions
Macromolecule
Conformations, Phase transitions,
Phonons, Solitons, Catalysis
Macromolecular complex
Collective modes,
Cooperative phenomena,
Multiple excitation
Cell
Metabolism, Signaling,
Trafficking, Individuality,
Differentiation
Energy levels
Energy landscape
Information + Construction
Instruction how to assemble
Parts
Assembler
Self reproducing
Information content
Information capacity : Nbd= bd
b = basis
d = digits
System
basis
4 letter words 26
Protein
20
Nucleic acid
4
digits
4
100
107
N
264
20100
410000000
bits
18.8
432
2·107
SOLIDS
PROTEINS
Periodic
Non-periodic
Disorder ↔ Random
Strong forces in all directions
Strong + weak
Local vibrations
Large motions
Energy levels
Energy landscape
Enormous number of states
Profound difference in
dynamic behavior
Elastic motions
Plastic motions
Time scale
Enormous number
Proteins
•20 building blocks, amino acids
•100-200 amino acids per protein (range from 15 to 3000)
•L-amino acids only!!!
•Large number of possible sequences
20100 to 20200 (this is practically infinity)
•For each sequence large number of conformations
2200 about 1060
•Instantaneous vs. average quantities
Proteins
Enzymes
Storage
Transport
Protection
Hormones
Structure
Light harvesting
Light production
Functions
Lysozyme, Ribonuclease,
LADH, Carbonic anhydrase
Ferritin, Ovalbumen, Caseine
Hemoglobin, Myoglobin
Hemocyanine
Antibodies, Fibrinogen,
TrombinHSP
Insulin, Growth factor
Collagen, α-Keratin
Rhodopsin, reaction centers
Luciferase
Packing Density of Proteins
Spheres 0.74
Cylinders 0.91
Solid
1.0
To function, proteins must be flexible.