For lecture 2, we will go deeper into the chemistry universe by starting to look at the electronic properties that explain all bonds and similar molecular interactions. We'll use the simplified concept of "orbitals" to examine bond formation, and discuss under what conditions we can approximate these complicated interactions that in principle require QM with classical models - it turns out that it will often work great for proteins. We'll look at the various interactions and particularly the "torsion" degrees of freedom that are important to determine the conformations of amino acids. The last interaction type is the so-called "nonbonded" ones, where we'll consider both electrostatics and so-called van der Waals interactions, examine why the latter always occur between atoms (induced dipole effects), and what their relative strengths are. We'll revisit hydrogen bonds and treat them slightly more formally in terms of the electronic interactions, and spend some time comparing the strength and importance of all these interactions. Already now, it seems that both very strong and very weak interactions can often be ignored (because we'll either "never" or "always" go over those barriers), while the intermediate strength ones are often most interesting - which prepares the ground for energy landscapes and distributions we'll consider in lecture 3.

Video recording of lecture

Playlist with short videos of concepts in lecture 02:

Modeling molecules with computers
All molecular interactions are due to electrons
Induced dipole-dipole interactions
Does this mean we need quantum chemistry?
Semi-empiric interaction models
Bonds and how to approximate unknown interaction forms
Units of energy in biomolecules
Angle interactions
Torsion (or dihedral) interactions
Potentials for torsions must be periodic
The phi/psi angles and Ramachandran diagrams (we'll revisit this)
Nonbonded interactions and their strengths
Partial charges on atoms in molecules
Van der Waals interaction forms: Buckingham and Lennard-Jones
A full potential function example
Hydrogen bonds in terms of orbitals, donor and acceptor atoms
Hydrogen bonds stabilise biomolecules
Introduction to hydrogen bonds in folding, and energy landscapes
Study questions

Lecture 02 recording as single video (1.5h)

Slides with still images from videos

(Some students found these useful to take notes)
Full-format stills
Handout-format stills

Reading instructions

Chapters 3-4 in the Protein Physics (1st edition at least) book, but it's not a perfect fit. We'll cover amino acids more in lecture 5!

Study questions

Why do chemical bonds form?
Even atoms with complete shells will eventually condense to liquids. Why?
What are the reasons you might need QM to describe biomolecular structure, and why not?
What is an orbital? How can you use the concept?
What is semi-empiric parametrisation? What’s the point of it?
What are the bonded interactions we typically use to describe e.g. structure in proteins?
Why do we use the bond/angle potentials we do?
Why does the torsion potentials have to be different?
What are the non-bonded interactions in a protein?
Can you name the two different forms of van der Waals interactions? How do they differ?
What interactions are strongest? Weakest?
What interactions do you have most of?
Compare electrostatics with dispersion. Strength? Importance at short/long distance?
What is partial charges? How do you get them?
Define the terms “donor” and “acceptor” for hydrogen bonds.
How is the concept of orbitals or “lone pairs” related to hydrogen bonds?
Where do hydrogen bonds occur in bimolecular structure?

Other videos

Cyrus Levinthal's Myoglobin visualization movie

Cyrus Levinthal's Lysozyme visualization movie

Scientific articles

Cyrus Levinthal's Scientific American article on the first visualizations of proteins

David Eisenberg's PNAS review on "the protein papers"