Molecular Dynamics Simulation of an Iron(III) Binding Site on the Fc Domain of IgG1 Relevant for Visible Light-Induced Protein Fragmentation

• DOI: 10.1021/acs.molpharmaceut.3c00612
• Publication Date: 2023-12-21T23:07:40Z
• Authors: Hao Lou; Yilue Zhang; Krzysztof Kuczera; Michael J. Hageman; Christian Schöneich
• Keywords: Fragmentation

Molecular dynamics simulations were employed to investigate the interaction between Fe(III) and an iron-binding site composed of THR259, ASP252, GLU261 on Fc domain IgG1. The goal was provide microscopic mechanistic information for photochemical, iron-dependent site-specific oxidative fragmentation IgG1 at THR259 reported in our previous paper. distance residues interest as well binding pocket size examined both protonated deprotonated THR259. free energy (ΔG) estimated by using umbrella sampling approach. pKa shift hydroxyl group caused presence nearby based a thermodynamic cycle. simulation results show that resides inside proposed profoundly changes configuration. ΔG values indicate possesses strong affinity Fe(III). Furthermore, lowers value 5.4 units.