Effect of H64V Mutation on the Dynamical Properties of Human Neuroglobin: A Simulation Study
In this work, we present a classical molecular dynamical simulation of human neuroglobin (Ngb) proteins with and without mutation at the distal position. Our aim is to investigate the role of the distal residue in the stability of Ngb. The simulation has
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Abstract
In this work, we present a classical molecular dynamical simulation of human neuroglobin (Ngb) proteins with and without mutation at the distal position. Our aim is to investigate the role of the distal residue in the stability of Ngb. The simulation has been performed using Gromacs software with Gromos96 force field. We designed a mutant Ngb by mutating histidine His64 residue to valine residue. The results showed that, the mutant H64V would lead to the less stability in the inner structure of the proteins. Moreover, the mutation strongly affects the properties of the heme group. Obvious changes in the high-order structure of the mutant protein can also be observed. Keywords
Neuroglobin
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Mutation
Introduction
Neuroglobin (Ngb) is a new member of the globin family discovered 15 years ago in the brain of vertebrates [1]. Ngb is not only expressed in the nervous system of vertebrates [1–4], but it is also present in retina, and other nerve tissues [5]. Ngb is composed of a single polypeptide of 151 amino acids and a heme prosthetic group which is able to bind to various gaseous ligands (O, NO or CO) at the central heme iron [6–10]. Ngb conserves two key histidine residues: a distal histidine His64 (E7) and a proximal histidine His96 (F8). In the absence of an external ligand, both histidines bind to the heme iron for the ferric (Fe3+) and the ferrous (Fe2+) forms of Ngb. Whereas, only His96 is in a hexacoordinated iron because it is close the coordination sphere of the heme iron atom. In this case, any external ligand competes with His64 (the sixth ligand in helix notation) for the binding of ferrous. An interesting feature of Ngb is the T.L.Q. Bui (&) Thai Binh University of Medicine and Pharmacy, 373 Lybon, Thai Binh, Vietnam e-mail: [email protected] V.T. Hoang T.-L.H. Nguyen V.T. Ngo Institute of Physics, VAST, 10 Daotan, Ba Dinh, Hanoi, Vietnam
MD simulation
existence of an intramolecular disulfide bond in the CD-D region involving two cysteine residues Cys46 (CD7) and Cys55 (D5). The S-S bridge plays an important role in regulating the activity and stability of protein. The experimental studies show an increase in CO rebinding rate and O2 affinity [11–14]. It is well known that the structure of a protein gives very important information about its roles and functions in the cell. From each structure, we can formulate the hypotheses about the role of particular amino acids within the protein. For testing these hypotheses, ones have to mutate specifically the gene which codes for the protein, and then analyze the mutant protein. Thus, in this work, we performed the classical simulations for the crystal proteins of wild-type H-Ngb and its mutation where the residue histidine is replaced by valine at position 64 of the protein.
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Material and Method
We have retrieved the 4MPM [15] Human Ngb data set from the protein data bank (PDB) as the input to perform the simulations. The presence of S-S disulfide bridge in Ngb-H was taken into account in this data. It is worth to notice that
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