title: A study on Fe(2+) - α-helical-rich keratin complex formation using isothermal titration calorimetry and molecular dynamics simulation.
abstract: Iron binding to protein is common in biological processes of dioxygen transport, electron transfer as well as in stabilizing drug-protein complexes. α-Helix is the most prevalent secondary structure of proteins. In this study, Fe(2+) binding to α-helix has been studied by isothermal titration calorimetry (ITC) and explicitly solvated molecular dynamics (MD) simulation. Ferrous gluconate and α-helix-rich keratin are used for the ITC study and the results revealed followed one set of identical sites binding model. The MD simulations further revealed that only the acidic side-chain functional groups and η(2) (O,O) coordination modes are involved in the binding of Fe(2+) to α-helix. The ITC results also showed that the binding of ferrous gluconate to keratin was entropy driven and the higher the temperature, the stronger the binding free energy. The favorable entropy of Fe(2+) binding to keratin was attributed to the displacement of water molecules on the α-helix surface, and was confirmed via MD simulations. The most stable coordination states of Fe(2+) and α-helix were identified via simulation: Fe(2+) stacks between two glutamic acid side chain carboxylate groups, displacing water molecules. The binding free energies calculated using MD simulation and the theoretical values were in excellent agreement with the ITC results.
authors: College of Engineering, China Agricultural University, Beijing, 100083, People's Republic of China.
authors: Yanyan
authors: Y
authors: Zhao
authors: Jan K
authors: JK
authors: Marzinek
authors: Peter J
authors: PJ
authors: Bond
authors: Longjian
authors: L
authors: Chen
authors: Qiong
authors: Q
authors: Li
authors: Athanasios
authors: A
authors: Mantalaris
authors: Efstratios N
authors: EN
authors: Pistikopoulos
authors: Massimo G
authors: MG
authors: Noro
authors: Lujia
authors: L
authors: Han
authors: Guoping
authors: G
authors: Lian
mesh_terms: D000818:Animals; D001665:Binding Sites; D002151:Calorimetry; D005296:Ferrous Compounds / Q000737:chemistry / Q000378:metabolism*; D007501:Iron / Q000737:chemistry / Q000378:metabolism*; D007633:Keratins / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012756:Sheep; D013816:Thermodynamics; D017186:Titrimetry
chemical_list: D005296:Ferrous Compounds; D007633:Keratins; D007501:Iron; C011819:ferrous gluconate
keywords: ITC; complexation; ferrous ion; keratin; molecular dynamics; protein binding; thermodynamics; α-helix