Fluctuation of the Solvent-Accessible Surface Area of Tuna Ferrocytochrome cChong Zheng, Chung F. Wong and J. Andrew McCammonBiopolymers, Vol. 29, Issue 14, pp. 1877-1883 (1990) [PubMed 2169921]The solvent-accessible surface area of proteins has an important
influence on the stability of protein folding and complexation.
Improperly folded structures often have solvation free energies larger
than the correctly folded ones, as estimated by empirical measures based
on contact surface areas. The solvent-accessible surface area is also
important in determining the rates of reactions that are preceded by
protein-protein or protein-ligand precursors such as electron transfer
reactions in cytochromes, or diffusion-controlled reactions in
myoglobin, superoxide dismutase, and carbonic anhydrase. Previous
analyses of protein surface areas have been based on static molecular
structures, usually those obtained by x-ray crystallography. The surface
features are, however, likely to be the most sensitive to crystal
packing effects. Also, a variety of theoretical and experimental studies
indicate that the largest fluctuations in proteins occur at their
surfaces. In this paper, we will therefore compare the
solvent-accessible surface area and its fluctuation from molecular
dynamics simulations with the surface area of the crystallographic
structure of tuna ferrocytochrome c, and analyze these quantities in
terms of time, energy, and possible biological consequences.
Point Charge Distributions and Electrostatic Steering in Enzyme/Substrate Encounter: Brownian Dynamics of Modified Copper/Zinc Superoxide DismutasesJacqueline J. Sines, Stuart A. Allison and J. Andrew McCammonBiochemistry, Vol. 29, No. 40, pp. 9403-9412 (1990) [PubMed 2248953]The electrostatic steering mechanism of bovine erythrocyte Cu/Zn
superoxide dismutase (SOD) was investigated through the use of Brownian
dynamics. Simulations of enzyme/substrate encounter were carried out on
14 different SOD models defined by simple changes in the enzyme's point
charge distribution. The magnitude and ionic strength dependence of
reaction rates, rates for collision anywhere on the enzyme surface, and
collision efficiency factors were analyzed to elucidate both the general
and specific roles for point charges associated with amino acid
residues. Collision rates for the general enzyme surface appear to be
solely determined by the net charge on the enzyme. At physiological
ionic strength this effect is negligible, with only 6% variation in
collision rates observed as the net charge ranges from +2e to -10e. With
the exception of a few charged residues in the active-site channel of
SOD, point charge modifications had modest effects on reaction rates.
For a large region within and surrounding the channel, reaction rates
increased or decreased by only 10-15% with the addition or subtraction
of a protonic unit of charge, respectively. This effect simply
disappeared with increasing distance from the active site. More dramatic
effects were seen at only three residues: arginine-141, glutamate-131,
and lysine-134. Implications for rate enhancement through site-directed
mutagenesis are discussed.