Binding mechanism of oseltamivir and influenza neuraminidase suggests perspectives for the design of new anti-influenza drugs
Fig 6
Free-energy landscape and the binding pathways of oseltamivir and NA.
(a) Free-energy landscape of oseltamivir along the NA surface. Collective variables x and y represent the projection of the distance vector between the centroids of oseltamivir and NA to the x-axis and y-axis of the system, respectively. The occurrence of the region with very low free energy in the upper right corner of the free-energy landscape will be explained in S1 Appendix, Section 2. (b) Top view of the sampling space of NA in the meta-eABF simulation. (c) Fusion image of NA conformation and free-energy landscape superimposed on Fig 6A and 6B. The metastable states are represented by circles and the pathways connecting the metastable states are shown as dashed lines. (d) Free-energy profiles as a function of the position (s) along the pathways. Pathway 1’: S7→S9, pathway 2’: S2→S7→S8→S9, pathway 3’: S6→S3→S9, pathway 4’: S0A→S2→S7→S9, pathway 5’: S0B→S2→S7→S9. S = 0.0 in pathways 1, 2, 3, 4 and 5 represents S7, S2, S6, S0A and S0B, respectively, and S = 1.0 in pathways 1, 2, 3, 4 and 5 represents S9.