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Locally Enhanced Sampling Molecular Dynamics Study of the Dioxygen Transport in Human Cytoglobin


Theoretical Molecular Biophysics Group
Institute of Physics, N. Copernicus University
87-100 Torun, Poland


Cytoglobin (Cyg) - a new member of the vertebrate heme globin family - is expressed in many tissues of human body but its physiological role is still unclear. It may deliver oxygen under hypoxia, serve as a scavenger of reactive species or be involved in collagen synthesis. This protein is usually six-coordinated and binds oxygen by a displacement of the distal His(E7) imidazole. In this article the results of 60 ns molecular dynamics (MD) simulations of dioxygen diffusion inside Cyg matrix are discussed. In addition to a classical MD trajectory an approximate Locally Enhanced Sampling method (LES) has been employed. Classical diffusion paths were carefully analyzed, five cavities in dynamical structures were determined and at least four distinct ligand exit paths were identified. The most probable exit/entry path is connected with a large tunnel present in Cyg. Several residues that are perhaps critical for kinetics of small gaseous diffusion were discovered. A comparison of gaseous ligand transport in Cyg and in the most studied heme protein myoglobin is presented. Implications of efficient oxygen transport found in Cyg to its possible physiological role are discussed.

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