Force-extension profile

The SMD simulations were based on an NMR structure of the Ig domain 127 of the cardiac titin I-band (Improta et ah, 1996). The Ig domains consist of two /9-sheets packed against each other, with each sheet containing four strands, as shown in Fig. 8b. After 127 was solvated and equilibrated, SMD simulations were carried out by fixing one terminus of the domain and applying a force to the other in the direction from the fixed terminus to the other terminus. Simulations were performed as described by Eq. (1) with V = 0.5 A/ps and if = 10 ksT/A 414 pN/A. The force-extension profile from the SMD trajectory showed a single force peak as presented in Fig. 8a. This feature agrees well with the sawtooth-shaped force profile exhibited in AFM experiments. 

Fig. 27. Mean force-extension profiles for 15-mer alanine obtained using SMD and EXEDOS methods (from Rathore et al. [32])...

The corresponding force-extension profiles for these calculations are shown in Fig. 27. The data presented for SMD and SMD-NH correspond to an individual trajectory. In order to arrive at a meaningful basis for comparisons between different schemes, the PMF for SMD and SMD-NH simulations is time averaged over 0.1 A(the bin width in EXEDOS), thereby reducing some of the statistical noise. For higher pulling rates (rates comparable to those employed in the literature), the forces and the PMF obtained from steered MD without a cantilever (SMD-NH) exhibit less noise than those obtained from... 

Using atomic force microscopy, it is possible to obtain the smooth force-extension profile of a single elastic model protein chain. 

Insertion of a globular protein sensing element within an elastic model protein chain results in a force-extension profile that contains the unfolding peak for the single globular protein. 

Binding of a single molecule to a highly selective site on the globular protein component can change the unfolding peak in the force-extension profile. 

To measure the force-extension law of a small biomolecule, these authors employed a two-step strategy. First, the background repulsive force-distance profile, in the absence of biomolecules, Fbg(h), is measured, h being the interparticle spacing. Then, once the biocomplexes have been properly attached within each interval between colloids, the same measurement is repeated, allowing determination of the force-distance profile of this irreversible assembly The force / >(/t)... 

Two Distinct Profiles of a Single-chain Force-extension Curve... 

Deviations of the force extension curves from FJC or WLC behavior, for example the kink in the force profile shown in Figure 8, often indicate conformational and configurational transitions along the polymer chain. As shown in Figure 8, Li and co-workers detected a force-induced chair-twist boat conformational transition, which cannot be measured by conventional methods, for a-(l,4)-linked polysaccharides (95). 

The simulation trajectory shown in Fig. 8b provides an explanation of how the force profile in Fig. 8a arises. During extension from 0 to 10 A the two /9-sheets slid away from each other, each maintaining a stable structure and its intra-sheet backbone hydrogen bonds. As the extension of the domain reached 14 A, the structure within each sheet began to break in one sheet, strands A and G slid peist each other, while in the other sheet, strands A and B slid past each other. The A -G and A-B backbone hydrogen bonds broke nearly simultaneously, producing the large initial force peak seen in Fig. 8a. 

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