Molecular dynamics simulation of the neuroglobin crystal: comparison with the simulation in solution

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biology

Background:

• Neuroglobin (Ngb) is a monomeric globin with a typical fold, featuring hexacoordinated ferric and ferrous forms.
• Ligand binding (O2, NO, CO) to ferrous Ngb causes structural changes, including heme sliding and cavity reorganization.

Purpose of the Study:

• To investigate the dynamical behavior of carbon monoxide-bound Neuroglobin (CO-Ngb) within a crystal environment.
• To compare crystal dynamics with previous solution-based simulations and experimental X-ray data.

Main Methods:

• 30 ns Molecular Dynamics (MD) simulations of CO-bound Ngb in a crystal.
• Comparison of simulation results with prior MD simulations in solution and X-ray crystallographic data.

Main Results:

• The crystal environment influences the dynamics of the heme group and the CD corner compared to solution.
• Heme oscillations observed in crystal simulations mirror crystallographic findings but with different occupancy.
• Ligand binding in solution affects CD corner flexibility, coupled to distal histidine configuration.

Conclusions:

• The protein's environment (crystal vs. solution) significantly impacts Neuroglobin's heme and CD corner dynamics.
• Understanding these environmental effects is crucial for interpreting Ngb's function and ligand interactions.