T. Haliloglu et I. Bahar, COARSE-GRAINED SIMULATIONS OF CONFORMATIONAL DYNAMICS OF PROTEINS - APPLICATION TO APOMYOGLOBIN, Proteins, 31(3), 1998, pp. 271-281
A coarse-grained dynamic Monte Carlo method is proposed for investigat
ing the conformational dynamics of proteins, Each residue is represent
ed by two interaction sites, one at the alpha-carbon, and the other on
the amino acid sidechain, Geometry and energy parameters extracted fr
om databank structures are used, The method is applied to the crystal
structure of apomyoglobin (apo-Mb). Equilibrium and dynamic properties
of ape-Mb are characterized within computation times one order of mag
nitude shorter than conventional molecular dynamics (MD) simulations.
The calculated rms fluctuations in alpha-carbons are in good agreement
with crystallographic temperature factors. Regions exhibiting enhance
d conformational mobilities are identified. Among the loops connecting
the eight helices A to H, the loop CD undergoes the fastest motions,
leading to partial unwinding of helix D. Helix G is the most stable he
lix on the basis of the kinetic stability of dihedral angles, followed
by the respective helices A, E, H, and B. These results, in agreement
with H/D exchange and two-dimensional NMR experiments, as well as wit
h MD simulations, lend support to the use of the proposed approach as
an efficient, yet physically plausible, means of characterizing protei
n conformational dynamics. (C) 1998 Wiley-Liss, Inc.