rerun of essentials of week 1-3

Rerun of essentials of week 1-3

Protein structure analysis, comparison, and prediction

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.

Non-bonded interactions

Lennard-Jones potential Coulomb potential

Protein detailsTorsion angle

Ramachandran plot

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 …

Hydrogen bonds

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

Salt bridgesSalt 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?).

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.

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*1.82~3200 J/Mole ~ 1kCal/Mole (again using Belgium calculus, that is)