Filtering out Low-Affinity Bitropic Ligands for Dopamine Receptors Based on Ligand Conformation.

We investigated the correlation between the conformations of a set of published 90 bitopic compounds on their affinity for two subtypes of the human dopamine receptor, D2R and D3R. Using molecular dynamics simulations, we showed that the compounds with large populations of compact conformation in the free solution are weak binders to both subtypes of the receptor. Our study provides a computational approach to quickly filter out low-affinity dopamine receptor ligands before their costly chemical synthesis.