1. Rerun of essentials of week 1-3 Protein structure analysis, comparison, and prediction

2. Structure comparison Structure relates to function. Structure comparison has the same role as sequence alignment: transfer of information. Done with structures, though, the transfer of information has much higher quality.

3. Non-bonded interactions Lennard-Jones potential Coulomb potential

4. Protein details Torsion angle Ramachandran plot

5. Action = Reaction Ramachandran plots for Glu and Asp found in loops. Who is who and why? Keep in mind that SFB is Bioinformatics 1 for the mature scientists …

6. Hydrogen bonds Paradoxically, hydrogen bonds are bad for the Folded Unfolded equilibrium (assuming we call folded good and unfolded bad…). Why?

7. Salt bridges Salt bridges work over a longer distance than other interactions (Coulomb goes with 1/r^2). So, salt bridges are easier to engineer than hydrogen bonds. This example shows a hydrogen bonded salt bridge. Salt bridges work less well in high salt solutions. (why?).

8. Cys-cys bonds Cysteine bridges are used for stability by small proteins, or by toxins that have to escape the innate immune system. Free cysteines are dangerous for a protein, so paired cysteines either don’t mutate or mutate in tandem. They either work thermodynamically by destabilizing the unfolded form, or kinetically by keeping surface loops from unfolding locally.

9. Accessibility Buried hydrophobic surface is worth about 20 J/Å2 (and don’t forget that there are two surfaces touching each other)… So, one carbon fully buried is worth 2*20*4*π*1.8 2 ~3200 J/Mole ~ 1kCal/Mole (again using Belgium calculus, that is)