Research Article
Physical quantity of residue electrostatic energy in flavin mononucleotide binding protein dimer

https://doi.org/10.1016/j.compbiolchem.2018.01.001Get rights and content

Highlights

  • The Electrostatic (ES) energy of each residue was first time quantitatively evaluated in flavin mononucleotide binding protein (FBP).

  • Among all residues, both Arg63 and Glu13 mainly contribute to Sub A–Sub B binding.

  • The FMN molecule greatly stabilizes the protein structure within a subunit.

  • The present work reveals that the ES energy not only plays an important role on ET phenomena but also in the protein stabilization in general.

Abstract

The electrostatic (ES) energy of each residue was for the first time quantitatively evaluated in a flavin mononucleotide binding protein (FBP). A residue electrostatic energy (RES) was obtained as the sum of the ES energies between atoms in each residue and all other atoms in the FBP dimer using atomic coordinates obtained by a molecular dynamics (MD) simulation. ES is one of the most important energies among the interaction energies in a protein. It is determined from the RES, the residues which mainly contribute to stabilize the structure of each subunit, and the binding energy between two subunits can be estimated. The RES of all residues in subunit A (Sub A) and subunit B (Sub B) were attractive forces, even though the residues contain net negative or positive charges. This reveals that the ES energies of any of the residues can contribute to stabilize the protein structure. The total binding ES energy over all residues among the subunits was distributed between −0.2 to −1.2 eV (mean = −0.67 eV) from the MD simulation time.

Introduction

The flavin mononucleotide binding protein (FBP) from Desulfovibrio vulgaris (Miyazaki F) is a small flavoprotein (Mw 13 kDa with 122 amino acids), which contains a flavin mononucleotide (FMN) as a cofactor (Kitamura et al., 1994). It is believed that FBP plays an important role in electron transport in the dark among proteins. The protein structure of FBP was determined by means of NMR spectroscopy in solution as being monomeric (Liepinsh et al., 1997) and with the X-ray diffraction method in crystal as being dimeric (Suto et al., 2000). It is now recognized that FBP is also a dimer in solution (Kitamura et al., 2007).

The phenomena of photoinduced electron transfer (ET) from tryptophanes (Trp) or tyrosines (Tyr) to an excited isoalloxazine (Iso*) has been often observed in flavoproteins (Chosrowjan et al., 2010). The ET rates have been obtained with the atomic coordinates of flavoproteins using the method of molecular dynamics (MD) simulation (Nunthaboot et al., 2011). In these works, it was pointed out that the net electrostatic (ES) energy between the photo-products and ionic groups inside the proteins has an important influence on the ET rates in the flavoproteins (Taniguchi et al., 2013; Nunthaboot et al., 2015).

It is known that the ES energy plays an important role in the ligand binding (Schutz and Warshel, 2001; Brenk et al., 2006). Moreover, it has been reported that the absolute values of the net ES energy markedly increases upon the dimer formation of FBP, and hence modifies the ET rates (Nunthaboot et al., 2016a). In the present work, we report the physical quantity of the ES energy for each residue (RES) in the FBP dimer for which atomic coordinates were obtained from the MD simulation in the explicit aqueous solution.

Section snippets

Methods of analyses

MD simulation was performed with the software package AMBER 10 (Case et al., 2008), and more details have been described elsewhere (Nunthaboot et al., 2016b). Briefly, the structure of the FBP dimer bound to the FMN is obtained from the Protein Data Bank (1FLM) (Suto et al., 2000) and used as the starting structures for the MD simulation. The amber FF03 force field (Wang et al., 2000) and the parameters developed by Schneider and Suhnel (Schneider and Sühnel, 1999) were used for the protein and

Dynamics and distributions of REST of some ionic residues

A snapshot of the protein structure of the wild type FBP dimer is shown in Fig. 2. The structures display a clear difference between Sub A and Sub B (Nunthaboot et al., 2016a). Fig. 3 shows the dynamics and distributions of REST of Glu13 obtained by eq. (1). The distances of Glu13 from Iso are 1.25 nm in Sub A and 1.51 nm in Sub B (Nunthaboot et al., 2016a). Fig. 3A shows the dynamics of REST (REST AA, REST AB, REST BA, and REST BB), where the REST AA denotes the REST of Glu13 in Sub A

Discussion

The ES energy of an individual residue inside a protein plays an important role, such as in ET phenomena or in the binding of a ligand (Schutz and Warshel, 2001; Brenk et al., 2006) to a protein. Among the interaction energies in a protein, the hydrogen bonding (H-Bond) energy is one of greatest energies, which is typically 10 kcal/mol (0.43 eV/pair). The RESs of most ionic groups are also very important, because they mostly displayed more than 0.43 eV. The dynamic behavior of the ES energy of

Conclusions

The ES energies of each individual residue of the FBP dimer whose atomic coordinates were obtained from MD simulation were quantitatively evaluated. The negative RES values revealed their contributions to stabilize the protein structure. Among all residues, both Arg63 and Glu13 mainly contributed to the Sub A–Sub B binding, while the FMN molecule greatly stabilizes the protein structure within a subunit. The present work reveals that the ES energy not only plays an important role in the ET

Acknowledgements

This work was financially supported by a research grant to promote the potential of lecturers and researchers, Mahasarakham University (fiscal year 2015). N.N. would like to acknowledge financial support from the Thailand Research Fund (MRG5380255) and the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Office of the Higher Education Commission, Ministry of Education. K.L. would like to thank RGJ Advanced Programme (RAP60K003). F.T. is thankful for a short-term visit grant from

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