09 July 2008

Primary Screening

What are people thoughts about primary screen methodology?

NMR, X-ray, Biochemical, MS, SPR, etc.


Don Emerson said...

As for primary fragment screening, I encourage a project teams to use bio-assay when possible. Certainly not all assays are able to reliably detect weak ligands and many suffer from background interference of colored or fluorescent compounds at high concentration. In some cases the use of a "kinetic read" helps with this. I then advocate follow-up with a biophysical assay such as NMR-STD, biacore, or ITD-calorimetry. In cases where the bioassay is not reliable and protein is abundantly available, you can reverse the order to put the biophysical assay first. In both cases, keep the X-ray step toward the end when there is a short list of validated hits with high ligand efficency, and solubility about 10-times above Kd.

Dr. Teddy Z said...

I agree with Don.

Joerg Kurt Wegner said...

Could someone please add some references and links to the mentioned statements or technologies?

I think not all readers might know all the buzz-words.

the fragment man said...

The bio-assay needs a verified readout. This is sometimes very difficult to get. And for orphan proteins...Just do the NMR!