Fig. 4: Examples of cryptic pockets and functionally relevant dynamics.
a,b, Conformational ensemble of Mpro (monomeric) predicts cryptic pockets near the active site (AS) and dimerization interface (DI). Conformational states (black circles) are projected onto the solvent-accessible surface areas (SASAs) of residues surrounding either the active site or the dimerization interface. The starting structure for simulations (6Y2E) is shown as a red dot. Representative structures are depicted by cartoons and transparent surfaces. Domains I and II are coloured cyan and domain III is coloured grey. The loop of domain III, which covers the active-site residues and is seen to be highly dynamic, is coloured red. c,d, The conformational ensemble from our simulations of nucleoproteins is similar to the distribution of structures seen experimentally. Conformational states are projected onto the distance and angle between the positive finger and a nearby loop. Angles θ were calculated between vectors that point along each red segment in d, and distances d were calculated between their centres of mass. Cluster centres are represented as black circles, the starting structure for simulations (6VYO) is shown as a red dot and NMR structures are shown as solid blue dots. Representative structures are shown as cartoons.
