Electrostatic Polarization Makes a Substantial Contribution to the Free Energy of Avidin−Biotin Binding

摘要

Abstract: Avidin biotin is one of the strongest protein ligand binding systems, with broad applications innbiomedical science. Here we report a quantum-based computational study to help elucidate the mechanismnof binding avidin to biotin (BTN1) and its close analogue, 2′-iminobiotin (BTN2). Our study reveals thatnelectronic polarization of protein plays a critical role in stabilizing the u0001 sheet (Thr113-Arg122) at the bindingnsite and makes a substantial contribution to the free energy of avidin biotin binding. The current finding isnin contradiction to the previous notion that electrostatic interaction has no effect on or makes an unfavorablencontribution to the free energy of avidin biotin binding. Our calculations also show that the difference innbinding free energy of avidin to BTN1 and BTN2 is almost entirely due to the contribution of electrostaticninteraction resulting from polarization-induced stabilization of a hydrogen bond between avidin and BTN1.nThe current result provides strong evidence that protein polarization accounts for the electrostatic contributionnto binding free energy that was missing in previous studies of avidin biotin binding.