Figure 2.

Transient exposure of Y88 in metadynamics simulations. (A) Time series of a CV that quantifies the number of contacts between Y88 and Cdk2 (CV VI, Table S2) in (upper panel) our single-walker, parallel-bias metadynamics simulation (Table S1, Ref. C) and (lower panel) a multiple-walker setup with eight replicas (Table S1, Ref. D). The average number of contacts calculated from our unbiased MD simulation is shown with a dashed line. (B) The number of contacts between Y88 (in gray) and its neighboring residues in Cdk2 (blue) is a good descriptor of the extent to which Y88 is buried in the active site or solvent exposed. (C) Shown are representative structures of a bound, native-like conformation of p27 structure with high coordination numbers (gray) and a conformation with a low coordination number in which Y88 and the entire D2.3 domain (green) (37) is unbound from Cdk2 active site (blue). No other major conformational changes are observed in bound p27. Time series for other CVs that we biased in the multireplica simulations are shown in Fig. S2. In this and other figures, a roman numeral in parentheses refers to the entries in Tables S2 and S3. To see this figure in color, go online.