Abstract
Cytoglobin (Cyg)—a new member of the vertebrate heme globin family—is expressed in many tissues of the 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 HisE7 imidazole. In this paper, 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 (LES) method 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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Acknowledgements
This work was supported by grant “Krok w przyszlosc-stypendia dla doktorantow” (S.O.), President of Poland grant “Superpracownia 2002” and in part by MEiN grant 2P04A 07229 (W.N.). We thank CI TASK for computer time and Albert Rutkowski for his assistance in computations.
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Fig. S1
RMSD analysis of all trajectories. The calculations were performed on Cα atoms using the initial structure as a reference. The blue plot represents the standard (LES1) trajectory. Black, red and green plots are from LES5, LES10 and LES15 trajectories, respectively (GIF 20 kb)
Fig. S2
Energy plots for the standard (LES1) trajectory, divided into total energy (black), kinetic (red) and potential (blue). The simulations are energetically stable (GIF 7 kb)
Fig. S3
Energy plots for the LES5 trajectory, divided into total energy (black), kinetic (red) and potential (blue). The simulations are energetically stable (GIF 7 kb)
Fig. S4
Energy plots for the LES10 trajectory, divided into total energy (black), kinetic (red) and potential (blue). The simulations are energetically stable (GIF 7 kb)
Fig. S5
Energy plots for the LES15 trajectory, divided into total energy (black), kinetic (red) and potential (blue). The simulations are energetically stable (GIF 7 kb)
Fig. S6
Temperature observed in the standard (LES1) trajectory. A value of the temperature achieved stabilization. The mean temperature is 299.72 ± 2.06 K (GIF 29 kb)
Fig. S7
Temperature observed in the LES5 trajectory. A value of the temperature achieved stabilization. The mean temperature is 299.74 ± 2.07 K (GIF 7 kb)
Fig. S8
Temperature observed in the LES10 trajectory. A value of the temperature achieved stabilization. The mean temperature is 299.74 ± 2.07 K (GIF 7 kb)
Fig. S9
Temperature observed in the LES15 trajectory. A value of the temperature achieved stabilization. The mean temperature is 299.74 ± 2.09 K (GIF 7 kb)
Fig. S10
Amino acids composition of the heme cavity (HemeCav). All phenylalanine residues are represented in red, leucines are displayed in green, Val85 in blue and His81 in yellow. The cytoglobin surface is represented in blue and the heme group with the proximal histidine is black (GIF 158 kb)
Fig. S11
All amino acids whose participate in building of the Xe1 cavity (CavXe1). All leucines are displayed in green and rest of the amino acids are properly labeled. The cytoglobin surface is represented in blue and the heme group with the proximal histidine is black (GIF 176 kb)
Fig. S12
All amino acids whose participate in building of the Xe4 cavity (CavXe4). The Cyg surface is represented in blue and the heme group with the proximal histidine is black (GIF 143 kb)
Fig. S13
All amino acids whose participate in building of the Xe2 Xe3 cavity (CavXe2Xe3). The color scheme is the same as on S10–S12 figures. Residue Ser128 is represented in pink, Val 93 is blue. The Cyg surface is represented in blue and the heme group with the proximal histidine is black (GIF 155 kb)
Fig. S14
All amino acids whose participate in building of the FE cavity (CavFE). The color scheme is the same as on previous figures. Residue Phe124 is represented in pink. The Cyg surface is represented in blue and the heme group with the proximal histidine is black (GIF 179 kb)
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Orlowski, S., Nowak, W. Locally enhanced sampling molecular dynamics study of the dioxygen transport in human cytoglobin. J Mol Model 13, 715–723 (2007). https://doi.org/10.1007/s00894-007-0203-x
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DOI: https://doi.org/10.1007/s00894-007-0203-x