We present hybrid ab initio QM/MM MD simulations and theoretical NMR chemical
shift calculations of the bilin chromophore phycocyanobilin (PCB) in the
binding pocket of the α-subunit of C-phycocyanin (α-C-PC). The good overall
agreement between the computed NMR chemical shifts and the experimental values
confirm the overall structural picture. A particular discrepancy is observed
for the pyrrole nitrogen and hydrogen on ring A, which points to a
disagreement between the reported X-ray structure and the experimental
solution-state NMR spectrum. Our results suggest that in the solution-state,
the binding pocket of α-C-PC slightly opens up allowing one water molecule to
form a stable bridge between ring A in PCB and the protein backbone at the
ASN73 residue. With this modified solution-state structure, the computed NMR
chemical shifts are in excellent agreement with experimental values. For
proteins still lacking a fully-resolved solution-state NMR-based structure,
this approach of combining ab initio MD/NMR provides a very sensitive probe
for local geometries at the sub-Ångstrom range that can be utilized to
compare/reconcile simple experimental one- and two-dimensional NMR data with
X-ray structures