[Update to Submission version May 2018: Substantial simplification of the theory/formalism sections for readability, improved incorporation of quadratic mixture model.]
Alchemical free energy perturbation is a rigorous technique the lab uses frequently for measuring ligand binding affinities. This new paper has an updated and simplified approach that we’ve developed over many years – motivated by challenges in measuring and interpreting binding affinities for membrane proteins. This approach even works for non-dilute reference state or a complex, phase-separated bulk! We’ve also included calculation of cholesterol affinities for 3 different GPCRs as a sample application.