Figure 1.

The mechanism of BPTU binding to the receptor–lipid interfacial pocket of P2Y₁ purinergic receptor (P2Y₁R) investigated by multiple computational simulation methods. (A) 1-(2-(2-(tert-butyl) phenoxy)pyridin-3-yl)-3-(4-(trifluoromethoxy)phenyl)urea (BPTU) molecules spontaneously penetrate and stay in Region II of the bilayer in unbiased molecular dynamics simulations. (B) The free energy surface (FES) underlying the BPTU–P2Y₁R association process and the proposed energetically favorable binding pathway. Four major energy minima found on the FES were labeled A–D. (C) The diagram of the funnel metadynamics simulation.