  We investigate protein-protein interactions in solution by small-angle X-ray
scattering (SAXS) and theoretical modeling. The structure factor for solutions
of bovine pancreatic trypsin inhibitor (BPTI), myoglobin (Mb), and intestinal
fatty acid-binding protein (IFABP) is determined from SAXS measurements at
multiple concentrations, from Monte Carlo simulations with a coarse-grained
structure-based interaction model, and from analytic approximate solutions of
two idealized colloidal interaction models without adjustable parameters. By
combining these approaches, we find that the structure factor is essentially
determined by hard-core and screened electrostatic interactions. Other soft
short-ranged interactions (van der Waals and solvation-related) are either
individually insignificant or tend to cancel out. The structure factor is also
not significantly affected by charge fluctuations. For Mb and IFABP, with small
net charge and relatively symmetric charge distribution, the structure factor
is well described by a hard-sphere model. For BPTI, with larger net charge,
screened electrostatic repulsion is also important, but the asymmetry of the
charge distribution reduces the repulsion from that predicted by a charged
hard-sphere model with the same net charge. Such charge asymmetry may also
amplify the effect of shape asymmetry on the protein-protein potential of mean
force.
