March 28

Question 1

When to use cocrystallization vs soaking?

Answer 1

For large ligand, and tight binding, use 1:1 concentration of ligand to protein, cocrystallition

or small ligand, use lots of it as many will bind per 1 protein, this is more like soaking. Avoid precipitants that will displace ligands

Question 2

How would you crystallize for lead generation in drug design?

Answer 2

Have crystal, then soak them with different compounds. If it dosen’t work, then do cocrystallization

Question 2

When deciding if your molecule can fit in region with lower electron density, what are temperature factor restraints?

Answer 2

Atoms bonded to eachother, expected to move in similar fasion.

Question 3

What 5 big things can use to judge quality of XRD model?

Answer 3

R-factor, Rfree
rms deviations from ideal bond lengths and angles
Ramachandran plot
Temperature factor plot
Luzzati Plot ( Has R-factor for observed and calculated model, higher factor means more similar. Then on x axis have 1 over resultion