Molecular dynamics simulations of the chromophore binding site of Deinococcus radiodurans bacteriophytochrome using new force field parameters for the phytochromobilin chromophore.

The conformational flexibility of the tetrapyrrolic phytochromobilin (PPhiB) chromophore of the bacteriophytochrome Deinococcus radiodurans (DrCBD) in the Pr state has been investigated by molecular dynamics simulations. Because these simulations require accurate force field parameters for the prosthetic group, in the present work we developed new empirical force field parameters for the PPhiB molecule that are compatible with the CHARMM22 force field for proteins. For this reason, the new force field parameters for the nonbonded (partial atomic charges) and bonded (bonds, angles, dihedrals, improper) energy terms were derived by reproducing ab initio target data following the methodology used in the development of the CHARMM22 force field. This new set of parameters was employed to analyze structural and dynamical features of PPhiB inside DrCBD. The 45 ns all-atom molecular dynamics (MD) simulation reveals the existence of two stable conformational states of the chromophore characterized by distinct torsional angles around the C-C bond at the methine bridge connecting rings A and B of the tetrapyrrole. This result supports experimental observations derived from NMR and resonance Raman spectroscopy. Furthermore, statistical analysis of H-bonding events allowed us to identify (a) important H-bonds between the propionic side chains of the chromophore and the apoprotein which may be relevant for the signal transduction step during the photoinduced cycle and (b) a network of eight water molecules which remain in the vicinity of the chromophore during the entire 45 ns production run.