The radicals derived from flavin adenine dinucleotide (FAD) are a corner stone of recent hypotheses about magnetoreception, including the compass of migratory songbirds. These models attribute a magnetic sense to coherent spin dynamics in radical pairs within the flavo-protein cryptochrome. The primary determinant of sensitivity and directionality of this process are the hyperfine interactions of the involved radicals. Here, we present a comprehensive computational study of the hyperfine couplings in the protonated and unprotonated FAD radicals in cryptochrome 4 from C. livia. We combine long (800 ns) molecular dynamics trajectories to accurate quantum chemistry calculations. Hyperfine parameters are derived using auxiliary density functional theory applied to cluster and hybrid QM/MM (Quantum Mechanics/Molecular Mechanics) models comprising the FAD and its significant surrounding environment, as determined by a detailed sensitivity analysis. Thanks to this protocol we elucidate the sensitivity of the hyperfine interaction parameters to structural fluctuations and the polarisation effect of the protein environment. We find that the ensemble-averaged hyperfine interactions are predominantly governed by thermally induced geometric distortions of the flavin. We discuss our results in view of the expected performance of these radicals as part of a magnetoreceptor. Our data could be used to parametrize spin Hamiltonians including not only average values but also standard deviations.