Solvent Effects On Protein Mechanical Stability: A Steered Molecular Dynamics Study

Quantum Mechanical and Molecular Mechanical Study of Solvent Effects

Steered molecular dynamics investigations of protein function.

Molecular recognition and mechanical properties of proteins govern molecular processes in the cell that can cause disease and can be targeted for drug design. Single molecule measurement techniques have greatly advanced knowledge but cannot resolve enough detail to be interpreted in terms of protein structure. We seek to complement the observations through so-called Steered Molecular Dynamics (...

The Mechanical Stability of the Titin Z1Z2/Telethonin Complex revealed by Steered Molecular Dynamics Simulations

The giant muscle protein titin, which provides a passive restoring force upon extension, is essential for maintaining the integrity of the muscular sarcomere. In order for titin to reversibly stretch and contract, the ends of this protein must be constrained, or anchored, at its terminal domains at the sarcomeric Z-disc and M-line. Here we investigate the role that telethonin, a protein which j...

Steered Molecular Dynamics

Steered molecular dynamics (SMD) induces unbinding of ligands and conformational changes in biomolecules on time scales accessible to molecular dynamics simulations. Time-dependent external forces are applied to a system, and the responses of the system are analyzed. SMD has already provided important qualitative insights into biologically relevant problems, as demonstrated here for application...

Steered Molecular Dynamics Simulations Predict Conformational Stability of Glutamate Receptors

The stability of protein-protein interfaces can be essential for protein function. For ionotropic glutamate receptors, a family of ligand-gated ion channels vital for normal function of the central nervous system, such an interface exists between the extracellular ligand binding domains (LBDs). In the full-length protein, the LBDs are arranged as a dimer of dimers. Agonist binding to the LBDs o...