Force induced conformation

Here we attempt to briefly introduce the principle of the AFM based SMFS and then focus on using SMFS to address three main questions force induced conformation transition, interaction between small molecules and polymers, and the interfacial conformation and adhesive energy of polymers. 

Given that our model system was smaller than the protein employed in the force-clamp AI experiments, the very first thing that needs to be proven is that the observed force-induced conformational rearrangement in the diethyl disulfide molecule can also take place in the protein and, thus, that the mechanism extracted from this model is responsible for the experimental findings reported for the protein. Force-field molecular dynamics simulations carried out on the same system used in... 

D. J. Muller, G. Biildt, and A. Engel, Force-induced conformational change of bacteriorhodopsin,/ Mol Biol, 249, 239-243 (1995]. 

Kumar, S., 8c Giri, D. (2005). Force-induced conformational transition in a system of interacting stiff polymers Application to unfolding. Physical Review E, 72, 052901. 

The rarity of the phenomenon of conformational polymorphism (one of the rare examples of conformational polymorphism is D,L-methionine (30)) is an indication that it is unusual for the crystal field forces to exercise a dominant influence on molecular conformation. It appears that the differences in the lattice sums of the crystal field forces for different conformations are in most cases an order of magnitude too small to induce conformational changes—i.e., tenths of kilocalorie per interaction rather than kilocalories. 

Mechanosensing is postulated to involve many different cellular and extracellular components. Mechanical forces cause direct stretching of protein-cell surface integrin binding sites that occur on all eukaryotic cells. Stress-induced conformational changes in the extracellular matrix may alter integrin structure and lead to activation of several secondary messenger pathways within the cell. Activation of these pathways leads to altered reg-... 

The equivalent of induced fit vs. conformational selection for the case of a motor protein is power stroke (a force-generating conformational change driven by a chemical reaction) vs. diffusion and catch (thermal fluctuation, even against an external force, followed by stabilization by chemical reaction). As we have discussed above, the distinction is meaningful only kinetically. For protein machines, the energy involved is not much greater than the thermal energy, and hence one cannot expect that one of the two processes overwhelms the other. 

It has recently become possible to alter the relation between force and [Ca +ji in myocardium, a useful trick in congestive heart failure. Pimobendan modestly increases the affinity of cardiac Tn C (cTn) for Ca +, thereby increasing the activation of contraction at any given [Ca +]i. The more potent levosimendan binds to the N-terminal region of cTn C in a Ca -dependent manner, and amplifies the effect of Ca +, perhaps by increasing the stability of the Ca +-induced conformational change in cTn C or by enhancing cooperativity in the thin filament. 

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