Computational investigation of conformational and spectroscopic substates in neuroglobin

The family of globins has a strong significance in the history of
protein research. Their abundance, spread in nature, and
evolutionary diversity are crucial factors for a wide range of approved and
suggested physiological functions taking place in almost every organism. The
versatility of ligand binding and unbinding and the tendency to act as a
catalyst for the oxidation of certain substrates in a selected number of
globins is strongly related to specific structural and dynamical properties
of the protein.
Neuroglobin, a structurally very related protein to myoglobin, is one
of several newly discovered globins which show some unique characteristics in
this family of proteins. Most importantly it was found that the heme prosthetic
group of the neuroglobin can become hexacoordinated to an internal histidine
residue in the absence of an exogenous ligand. This feature, which is meant to
control the affinity for external ligand binding, lead to many speculations
about the physiological function of neuroglobin. Some suggested functions
involve enhanced oxygen supply in neuronal cells, regulation of hypoxia, and
radical scavenging.
Here, a collection of specialized molecular dynamics methods is used to
investigate the structural and dynamical peculiarities of neuroglobin in more
detail. Multipolar force fields are used to energetically, dynamically and
spectroscopically determine the migration network of CO in photolyzed
carbonmonoxy neuroglobin. A combination of classical molecular dynamics and
quantum mechanical techniques elucidate the conformational
substates of carbonmonoxy neuroglobin which are experimentally accessible with
infrared spectroscopy. Furthermore, the nature of the configurational
transitions occurring during the competition for internal and external ligand
binding are analyzed by the adiabatic reactive molecular dynamics method.