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Phys 210: May 19, 2014 Modern Physics Structural Biology

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Page 1: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Phys 210: May 19, 2014

● Modern Physics– Structural Biology

Page 2: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Class Comments

● Quiz 11 will open today– Will have questions based on todays lecture

Page 3: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

LENGTH SCALES(wikipedia)

Page 4: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Structural Biology(from wikipedia)

Structural biology is a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations in their structures affect their function. This subject is of great interest to biologists because macromolecules carry out most of the functions of cells, and because it is only by coiling into specific three-dimensional shapes that they are able to perform these functions. This architecture, the "tertiary structure" of molecules, depends in a complicated way on the molecules' basic composition, or "primary structures."

Page 5: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Cells● The cell is the basic structural, functional and

biological unit of all known living organisms. Cells are the smallest unit of life that can replicate independently, and are often called the "building blocks of life".

SCALE Micrometers10E-6 meters

Page 6: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Biomolecules are cellular building blocks

● Molecule: collection of atoms covalently bound together.

● Four classes of biomolecules

Page 7: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Atoms

Page 8: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Atoms and Moleculesscale atomic radius:

Quantum mechanics can tell us about the interactions between nuclei and electrons

Classical mechanics can tell us about the interactions between atoms

Page 9: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Water

Page 10: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Molecular Interactions

Scales: 1 nm = 10 E-9 meters

Atomic Radius ~ Angstrom = 10E-10 meters

Size of Cell ~ micro meters = 10E-6

Page 11: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Sugars: Store Energy

Page 12: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Fatty Acids: Make membranes

Page 13: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Fatty Acids and Membranes

Page 14: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Amino Acids and Proteins

● The 20 amino acids and a peptide bond

Page 15: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

The 20 Amino Acids

Page 16: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Protein Structure

Page 17: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Protein Structure

● Primary●

● Secondary●

● Tertiary●

● Quartenary

Page 18: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Nucleic Acids and DNA/RNA

● DNA = deoxyribonucleic acid● RNA = ribonucleic acid● Both have a phosphodiester backbone● hydrogen bonding make two strands into

dsDNA.

Page 19: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Structure of DNA

Page 20: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

DeoxyriboNucleicAcid

DNA : The Genetic Stuff

Page 21: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

DeoxyriboNucleicAcid

DNA : The Genetic Stuff

Page 22: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Chem. & Eng. News; July 17, 2006

The Human Genome is 3,000,000,000 basepairs long.That's one meter long.

It is stored as 23 pairs of chromosomes... so there is actually 2m of DNA in every cell of your body!

Page 23: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Felsenfeld, Nat. 2003Luger Nat. 1997

DNA Folding

Page 24: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Zlatanova and LeubaJMB 2003

Luger, 1997Schalch Nature 2005

Bednar, PNAS 1998

Biology 101Nucleosomes and Chromatin

Page 25: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Energy Landscape

Page 26: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Molecular Biology Dogma

● Sequence → Structure → Function

● Applies to nucleic acids as well as amino acids.

Page 27: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Experimental Methods

● X-ray crystallography– Diffraction of x-rays from crystals of protein and/or DNA

– See the Protein Data Bank

● Separation Techniques– Gel mobility:

● Depends on “holes” in gel and on shape + charge of molecule

● Single Molecule Force Spectroscopy– Can't see it but can feel it.

Page 28: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

X-ray Crystallography

Page 29: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

X-ray CrystallographyMyoglobin first protein Structure to be determined by X-ray crystallography. 1950

Page 30: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Electrophoresis

Page 31: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Atomic Force Spectroscopy

Page 32: Phys 210: May 19, 2014 · Phys 210: May 19, 2014 ... biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations

Modeling Methods

● Quantum Mechanics– Solves the Schrodinger Equation and thus gives information

about the electronic structure

● Molecular Mechanics– Solves Newtons equations using approximate models for the

ineractions between molecules. This is classical mechanics.● Each atom is a ball with radius (occupies space)● Atoms connected by springs● Atoms have “partial charge” even for neutral atom