The role of molecular size in ligand efficiency.
Ligand efficiency is a simple metric for assessing whether a ligand derives its potency from optimal fit with the protein target or simply by virtue of making many contacts. Comparison of protein-ligand binding affinities for over 8000 ligands with 28 protein targets shows conclusively that the average ligand binding affinities are not linear with molecular size. It is therefore important to scale ligand efficiencies by the size of the ligand, particularly where small ligands (e.g., fragments) are involved. We propose a simple 'fit quality' metric that removes this dependence.
Reynolds
Charles H
CH
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, PO Box 776, Spring House, PA 19477, USA. CReynoll@prdus.jnj.com
Bembenek
Scott D
SD
Tounge
Brett A
BA
D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*
D008024:Ligands; D011506:Proteins