Molecular dynamics (MD) simulations have been carried out for 62.5 ps
on crystal structures of deoxy sickle cell hemoglobin (HbS) and normal
deoxy hemoglobin (HbA) using the CHARMM MD algorithm, with a time ste
p of 0.001 ps. In the trajectory analysis of the 12.5-62.5 (50 ps) sim
ulation, oscillations of the radius of gyration and solvent-accessible
surface area were calculated. HbS exhibited a general contraction dur
ing the simulation, while HbA exhibited a nearly constant size. The av
erage deviations of simulated structures from the starting structures
were found to be 1.8 angstrom for HbA and 2.3 angstrom for HbS. The av
erage rms amplitudes of atomic motions (atomic flexibility) were about
0.7 angstrom for HbA and about 1.0 angstrom for HbS. The amplitudes o
f backbone motion correlate well with temperature factors derived from
x-ray crystallography. A comparison of flexibility between the alpha-
and beta-chains in both HbA and HbS indicates that the beta-chains ge
nerally exhibited greater flexibility than the alpha-chains, and that
the HbS beta-chains exhibit greater flexibility in the N-terminal and
D- and F-helix regions than do those of HbA. The average amplitude of
backbone torsional oscillations was about 9-degrees, a value comparabl
e with that of other simulations, with enhanced torsional oscillation
occurring primarily at the ends of helices or in loop regions between
helices. Comparison of atomic flexibility and torsional oscillation re
sults suggests that the increased beta-chain flexibility results from
relatively concerted motions of secondary structure elements. The incr
eased flexibility may play an important role in HbS polymerization. Ti
me course analysis of conformational energy of association, hydrogen b
onding and hydrophobic bonding (as calculated from solvent accessibili
ty) shows that all three of these factors contribute to the stability
of subunit association for both hemoglobins.