Coarse-grained simulations of conformational dynamics of proteins: application to apomyoglobin

A coarse-grained dynamic Monte Carlo method is proposed for investigating the conformational dynamics of proteins. Each residue is represented by two interaction sites, one at the alpha-carbon, and the other on the amino acid sidechain. Geometry and energy parameters extracted from databank structures are used. The method is applied to the crystal structure of apomyoglobin (apo-Mb). Equilibrium and dynamic properties of apo-Mb are characterized within computation times one order of magnitude shorter than conventional molecular dynamics (MD) simulations. The calculated rms fluctuations in alpha-carbons are in good agreement with crystallographic temperature factors. Regions exhibiting enhanced 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 helix 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 with MD simulations, lend support to the use of the proposed approach as an efficient, yet physically plausible, means of characterizing protein conformational dynamics.