Journal
ACS CHEMICAL BIOLOGY
Volume 10, Issue 10, Pages 2237-2245Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.5b00378
Keywords
-
Categories
Ask authors/readers for more resources
DNA encoded library (DEL) technology allows for rapid generation of extremely large numbers of small molecules and is often used to find novel chemical starting points for pharmaceutically relevant proteins. DEL selection output consists of a list of small-molecule structures and enrichment levels. It is widely presumed that molecules with greater enrichment will have larger equilibrium association constants, and follow-up efforts are triaged accordingly. Herein we describe a simple mathematical model used to simulate DEL selections. Simulations predict that enrichment levels will correlate poorly with equilibrium association constants when selections use high concentrations of protein or lower quality DELs (high variance in final product synthetic yields). A potentially superior technique is demonstrated to qualitatively assess equilibrium association constants directly from sequencing data. This technique requires conducting selections over a range of protein concentrations, so that the influence of synthetic yield can be accounted for.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available