Topology and thermodynamics of gaseous ligands diffusion paths in human neuroglobin

The physiological role of recently discovered human neuroglobin (Ngb) is still unknown. Sound hypothesis says that it protects brain during hypoxia. In this paper the advanced potential of mean force by implicit ligand sampling (PMF/ILS) method is used to study the free energy landscape of Ngb for O 2, NO and CO ligands. The multiple diffusion paths are discovered and four ligand binding cavities are determined. The data show that certain regions are easily accessible by O 2 and NO but are protected from CO. Free energy landscapes provide realistic data for stochastic models of ligand diffusion in proteins.