To understand the connection between the conformation of a protein molecule and the oxidation of its methionine residues, we measured the rates of oxidation of methionine residues by H2O2 in granulocyte colony-stimulating factor (G-CSF) as a function of pH and also studied the structural properties of this protein as a function of pH via molecular dynamics simulations. We found that each of the four methionine groups in G-CSF have significant and different rates of oxidation as a function of pH. Moreover, Met1, in the unstructured N-terminal region, has a rate of oxidation as low as half that of free methionine. The structural properties of G-CSF as a function of pH are evaluated in terms of properties such as hydrogen bonding, deviations from X-ray structure, helical/helical packing, and the atomic covariance fluctuation matrix of α-carbons. We found that dynamics (structural fluctuations) are essential in explaining oxidation and that a static picture, such as that resulting from X-ray data, fails in this regard. Moreover, the simulation results also indicate that the solvent-accessible area, traditionally used to measure solvent accessibility of a protein site, of the sulfur atom of methionine residues does not correlate well with the rate of oxidation. Instead, we identified a structural property, average two-shell water coordination number, that correlates well with measured oxidation rates.