Phys 210: May 19, 2014

● Modern Physics– Structural Biology

Class Comments

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

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LENGTH SCALES(wikipedia)

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."

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

Biomolecules are cellular building blocks

● Molecule: collection of atoms covalently bound together.

● Four classes of biomolecules

Atoms

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

Water

Molecular Interactions

Scales: 1 nm = 10 E-9 meters

Atomic Radius ~ Angstrom = 10E-10 meters

Size of Cell ~ micro meters = 10E-6

Sugars: Store Energy

Fatty Acids: Make membranes

Fatty Acids and Membranes

Amino Acids and Proteins

● The 20 amino acids and a peptide bond

The 20 Amino Acids

Protein Structure

Protein Structure

● Primary●

● Secondary●

● Tertiary●

● Quartenary

Nucleic Acids and DNA/RNA

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

dsDNA.

Structure of DNA

DeoxyriboNucleicAcid

DNA : The Genetic Stuff

DeoxyriboNucleicAcid

DNA : The Genetic Stuff

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!

Felsenfeld, Nat. 2003Luger Nat. 1997

DNA Folding

Zlatanova and LeubaJMB 2003

Luger, 1997Schalch Nature 2005

Bednar, PNAS 1998

Biology 101Nucleosomes and Chromatin

Energy Landscape

Molecular Biology Dogma

● Sequence → Structure → Function

● Applies to nucleic acids as well as amino acids.

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Experimental Methods

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

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– 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.

X-ray Crystallography

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

Electrophoresis

Atomic Force Spectroscopy

Modeling Methods

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

about the electronic structure

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● 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