tailieunhanh - Atomic Force Microscopy in Cell Biology Episode 2 Part 8

Tham khảo tài liệu 'atomic force microscopy in cell biology episode 2 part 8', kỹ thuật - công nghệ, cơ khí - chế tạo máy phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả | 326 Altmann and Lenne may be interpreted as to represent a projection of a large volume of configuration space onto one of two preferred tracks. Paci and Karplus 1999 found two sets of unfolding pathways for fibronectin-type 3 modules by molecular dynamics simulations which are analogous to those that we propose. The same authors have recently detected stable intermediates during unfolding of a single-spectrin domain Paci and Karplus 2000 . Both tracks follow similar directions in real space as defined by the direction of the applied force however according to our model they may lead to two different unfolded states starting from the native folded state Fig. 11 . The intermediate state is conceptually available along both pathways but each pathway by itself either leads from the native state 0 to the partially unfolded state 1 or the completely unfolded state 2. The relative difference of the height of the free energy barrier along either of the two pathways determines whether state 1 or state 2 is attained. The advantage of this strongly simplified modeling is that only one free parameter is needed for differentiating between the two averaged pathways. At the same time we find this approach to be in good agreement with our data from the experiment and from Monte Carlo MC simulations see following . In the native folded state the protein is in state 0 at the bottom of the potential well. The directional mechanical stress applied by the AFM tip not only decreases the barrier height to thermally activated unfolding but also reduces the options of the protein to those of following either path 1 or path 2 during unfolding. The protein will follow only one path leading to a bimodal probability distribution with 35 and 65 probabilities for path 1 and path 2 respectively according to our experimental data. The external stretching force reduces the effective energy barriers so that the system can cross them by thermal activation Evans and Ritchie 1997 . As the applied .