Forced unfolding simulation

Forced unfolding simulations have also been applied to globular proteins to determine whether the unfolding response mimics that observed for... 

The first, CLN025, was refolded from a partially unfolded conformation obtained through forced unfolding simulations, and the second refolded from putative TS structures generated by elevated temperature simulations. Although the -hairpin from protein G successfully refolded through an initial hydrophobic collapse, that of CLN025 misfolded to an unstable hairpin-like state. ... 

Paci, E. Karplus, M., Forced unfolding of fibronectin type 3 modules. An analysis by biased molecular dynamics simulations, J. Mol. Biol. 1999, 288, 441 —459... 

E. Paci and M. Karplus, J. Mol. Biol., 288, 441 (1999). Forced Unfolding of Fibronectin Type 3 Modules An Analysis by Biased Molecular Dynamics Simulations. 

R. Toofanny and P. M. Williams, J. Mol. Graph. Model., 24, 396 (2006). Simulations of Multi-Directional Forced Unfolding of Titin 127. 

Lu, H. Schulten, K., Steered molecular dynamics simulations of force-induced protein domain unfolding, Proteins Struct. Funct. Gene. 1999, 35, 453 163... 

It is, however, important to note what might be accomplished if the growth rate calculated above can be continued for another 10-20 years. If this happens, simulations on proteins with 100-200 residues can be expected to reach into the millisecond domain, and simulations covering a full second would be attainable within about twenty years. Recent demonstrations of the accuracy of modern molecular force fields [62,63] hold the promise that unbiased molecular dynamics simulations could follow the folding process all the way from the completely unfolded state to the native state, a truly exciting prospect. 

Standard molecular mechanics (MM) force fields have been developed that provide a good description of protein structure and dynamics,21 but they cannot be used to model chemical reactions. Molecular dynamics simulations are very important in simulations of protein folding and unfolding,22 an area in which they complement experiments and aid in interpretation of experimental data.23 Molecular dynamics simulations are also important in drug design applications,24 and particularly in studies of protein conformational changes,25,26 simulations of the structure and function of ion channels and other membrane proteins,27-29 and in studies of biological macromolecular assemblies such as F-l-ATPase.30... 

Applying an all-atom parallel tempering simulation of the protein HP-36 in the ECEPP/2 force field [33] using an implicit solvent model [34] the authors of [27] have measured the diffusion of labeled replicas in temperature space. The simulated temperature interval is chosen such that at the lowest temperature = 250 K the protein is in a folded state and the highest temperature T ax = 1000 K ensures that the protein can fully unfold for the simulated force field. The measured local diffusivity for the random walk between these two extremal temperatures is shown in Fig. 7. A very strong modulation of the local diffusivity is found along the temperature. Note the logarithmic scale of the ordinate. The pronounced minimum of the local diffusivity around T 500 K points to a severe bottleneck in the simulation which by measurements of the specific heat has been identified as the helix-coil... 

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