Figure 2. Conformational landscape of c-src tyrosine kinase.

The conformational landscape generated using RMSD of A-loop residues (404-424) and difference of the distance between Glu310-Arg409 and Lys295-Glu310 residue pairs as the order parameters reveals multiple intermediates along the activation pathway. The free energy values are reported in kcal mol⁻¹. The landscape is obtained by summing over all the micro-states of the 2000 state MSM from i=1 to N using the following equation $W(x,y)=k_B\mathit{\text{Tln}}[{\sum }_i^N{\pi }_i{h}_i(x,y)]$ where π_i is the probability of state i in the MSM, and h_i(x, y) is the normalized histogram of the variables x and y restricted to the MSM state i.