N. Kurt et T. Haliloglu, Conformational dynamics of subtilisin-chymotrypsin inhibitor 2 complex by coarse-grained simulations, J BIO STRUC, 18(5), 2001, pp. 713-731
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.