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.