Bone morphogenetic protein-2 (BMP-2) plays a crucial role in osteoblast differentiation and proliferation. Its effective therapeutic use for ectopic bone and cartilage regeneration depends, among other factors, on the interaction with the carrier at the implant site. In this study, we used classical molecular dynamics (MD) and a hybrid approach of steered molecular dynamics (SMD) combined with MD simulations to investigate the initial stages of the adsorption of BMP-2 when approaching two implant surfaces, hydrophobic graphite and hydrophilic titanium dioxide rutile. Surface adsorption was evaluated for six different orientations of the protein, two end-on and four side-on, in explicit water environment. On graphite, we observed a weak but stable adsorption. Depending on the initial orientation, hydrophobic patches as well as flexible loops of the protein were involved in the interaction with graphite. On the contrary, BMP-2 adsorbed only loosely to hydrophilic titanium dioxide. Despite a favorable interaction energy between protein and the TiO(2) surface, the rapid formation of a two-layer water structure prevented the direct interaction between protein and titanium dioxide. The first water adlayer had a strong repulsive effect on the protein, while the second attracted the protein toward the surface. For both surfaces, hydrophobic graphite and hydrophilic titanium dioxide, denaturation of BMP-2 induced by adsorption was not observed on the nanosecond time scale.

No abstract

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.

No abstract

No abstract