title: Tunable nanomechanics of protein disulfide bonds in redox microenvironments.
abstract: Disulfide bonds are important chemical cross-links that control the elasticity of fibrous protein materials such as hair, feather, wool and gluten in breadmaking dough. Here we present a novel computational approach using the first-principles-based ReaxFF reactive force field and demonstrate that this approach can be used to show that the fracture strength of disulfide bonds is decreased under the presence of reducing agents, due to a loss of cross-link stability controlled by the chemical microenvironment. Simulations in explicit solvents and dithiothreitol (DTT) indicate an intermediate step involving weakened elongated bonds, illustrating the tunability of the elasticity, rupture mechanism and strength of proteins. We provide a mechanistic insight into the fracture mechanism of protein disulfide bonds and illustrate the importance of the redox microenvironment, where factors such as accessibility, mechanical strain and local redox potential govern the dominating rupture mechanism and location. The method used here provides a general computational protocol for studying mechanochemical fracture of large-scale protein materials concurrently with experimental efforts.
authors.affiliation: Laboratory for Atomistic and Molecular Mechanics, Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Room 1-235A&B, Cambridge, MA 02139, United States.
authors.forename: Sinan
authors.initials: S
authors.lastname: Keten
authors.forename: Chia-Ching
authors.initials: CC
authors.lastname: Chou
authors.forename: Adri C T
authors.initials: AC
authors.lastname: van Duin
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Buehler
mesh_terms: D001696:Biomechanical Phenomena; D020916:Conotoxins / Q000737:chemistry* / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D055595:Mechanical Phenomena; D056004:Molecular Dynamics Simulation; D036103:Nanotechnology / Q000379:methods*; D010084:Oxidation-Reduction; D011487:Protein Conformation; D012997:Solvents / Q000737:chemistry; D014783:Viscosity
chemical_list: D020916:Conotoxins; D004220:Disulfides; D012997:Solvents