By applying each external load

By applying each external load to the G-actin molecule, and measuring the elongation of the molecule, we computed force-displacement curves. The force versus displacement curve can be used to evaluate the tensile stiffness of the G-actin from a linear regression analysis. Followed by statistical analysis over each set of three stiffness values extracted from the same spring probe, a unique per k used was estimated. Finally, in order to determine the effective molecular stiffness spring constant, the stiffness values were plotted versus the virtual kSMD values and convergence was analyzed. As performing tensile test requires some fixed atoms, in each three case of studies, some of the atoms are fixed. In the axial tensile test, some C atoms at the bottom of the G-actin are fixed. These fixed atoms and SMD atoms are selected in a way that G-actins interact in F-actin and the interacting atoms are considered as reported in Ref. Holmes et al. (1990). When a filament undergoes an axial tensile test, the tensile force is transmitted through the filament by the interacting atoms which connect the consisting monomers. Therefore, the interacting atoms at the monomers are the main component of exerting force to the monomer. Hence, the interacting atoms at the bottom of the Letermovir (subdomains 1 and 3) are considered as the fixed atoms while the tensile force is supposed to apply at the interacting atoms at the top of the monomer (subdomains 2 and 4). The interacting atoms at the filament for two adjacent monomers is reported in Ref. Holmes et al. (1990). In lateral loading, selection of the fixed is considered same as interacting atoms at the F-actin, however, SMD atoms are considered as interacting atoms of a G-actin and Arp2/3 complex which have been reported in Ref. Goley et al. (2010). More precisely, for the monomer in the mother filament, the interacting atoms of the three sequential monomers are not allowed to move freely. Therefore, this restriction makes them a great candidate for the fixed atoms of the SMD simulation. Moreover, when the tensile force is applied to the daughter filament, the force is transmitted to the mother filament by the interacting atoms and one should bear in mind that we have chosen these atoms to be subjected to the tensile force. For the sake of better understanding, Table 1, presents the residue number of the interacting atoms in the axial and lateral test and also SMD and fixed atom in both axial and lateral cases are depicted in Fig. 3.
Results and discussion As it was aforementioned, both systems were equilibrated for 1ns. The root mean-square deviation (RMSD) of C atoms from the initial x-ray structures are about 3.47Å for ATP state and 3.46Å for ADP state. In this section, each system is simulated via SMD method in order to evaluate the tensile stiffness in the different direction as illustrated in Fig. 2. In the following, first, the axial tensile test is presented in Section 4.1 and then Section 4.2 devoted to the reporting the results of the lateral tensile test.
Actin-actin bond breaking force In this section, breaking force of the actin-actin bond under tension test is investigated. To do so, constant velocity SMD is employed to perform a tensile test on the actin filament. The procedure to evaluate the breaking force of actin-actin bond is illustrated in Fig. 10. As depicted in the latter figure, 4 monomers of an actin filament are selected and the simulation consists of two individual steps. In the first step, two monomers are moved by constant velocity in an aqueous solution and the required force is extracted (F2mon). Next, 4 monomers consisting a filament are simulated and by applying a tension force to the two of them and fixing the two other monomers, the pulling force is extracted (F4mon). Finally, one should bear in mind that the breaking force of actin-actin bond can be calculated by subtracting the two obtained forces, namely, F2mon and F4mon.