Conformational dynamics of subtilisin-chymotrypsin inhibitor 2 complex by coarse-grained simulations

An off-lattice dynamic Monte Carlo (MC) method is used to investigate the c onformational dynamics of chymotrypsin inhibitor 2 (CI2) and subtilisin in both free and complex forms over two time windows, referring to short and l ong time scales. The conformational dynamics of backbone bonds analysed fro m several independent trajectories reveal that: Both the inhibitor and the enzyme are restricted in their bond rotations, excluding a few bonds, upon binding; the effect being greatest for the loop regions, and for the inhibi tor. A cooperativity in the near-neighbor bond rotations are observed on bo th time scales, whereas the cooperative rotations of the bonds far along th e sequence appear only in the long time window, and the latter time window is where most of the interactions between the inhibitor and the enzyme are observed. Upon binding, the cooperatively rotating parts of the inhibitor a nd the enzyme are readjusted compared to their free forms, and new correlat ions appear. The binding loop, although it is the closest contact region, i s not the only part of the inhibitor involved in the interactions with the enzyme. Loops 3 and 8 and the helices F and G in bound enzyme and the bindi ng loop of the inhibitor contribute at the most to the collective motions o f whole structure on the slow time scale and are apparently important for e nzyme-inhibitor interactions and function. The results in general provide e vidence for the contribution of the loops with cooperative motions to the e xtensive communication network of the complex.