Identification of plant α-tubulin amino acids playing a key role in specific binding of nitroaniline compounds

Abstract

Aim. Computational prediction of amino acid residues critical for specific binding of nitro- and dinitroaniline compounds in plant α-tubulin. Methods. Protein structure modeling (I-Tasser, Grid-computing) and ligand library preparation, molecular docking (CCDC Gold), molecular dynamics (MD, Gromacs computing in Grid). Evaluation of the amino acid ensemble associated with ligand binding based on results of MD energy perturbations of protein-ligand complex. Results. The structural model of plant α-tubulin from Avena sativa was build. Also, the virtual library of 25 nitroaniline compounds was prepared. The docking of ligands into the interdimer contact of α-tubulin and MD simulations of the leading complexes reveal differences in ligands conformational energy during the exchange between free and binding states. The mean number of hydrogen bonds and dynamics of their formation in complex were compared. These computations allow us to select a.a. residues playing key role in specific interaction with nitro- and dinitroaniline compounds in plant α-tubulin. Conclusions. Computational prediction specify 28 a.a. residues playing the main role in binding of nitro- and dinitroaniline compounds with plant α-tubulin from Avena sativa: Arg2, Glu3, Ile4, Cys129, Thr130, Gly131, Leu132, Gln133, Gly134, Gly162, Lys163, Lys164, Ser165, Leu242, Arg243, Asp245, Gly246, Ala247, Ile248, Asn249, Val250, Asp251,Val252, Thr253, Glu254, Phe255, Thr257, Asn258.
 Keywords: plant, α-tubulin, nitroaniline compounds, molecular docking, molecular dynamics, ligand binding.

Unveiling the Possible Oryzalin-Binding Site in the α-Tubulin of Toxoplasma gondii

“… 14 , 19 − 21 Meanwhile, other studies have proposed that ORYbs might be located on top of the N-loop near to the β-tubulin interface (see Figure 1 D). 22 − 24 Unfortunately, these proposed binding sites are found in poorly accessible regions, away from amino acids with known OR mutations or comprise several highly conserved residues between ORY-susceptible and non-susceptible organisms.…”

“…Based on the OR mutation data and computational results, several research groups have proposed different ORY binding sites (ORYbs) in α-tubulin of plants and protozoan parasites. Some of these groups have suggested that dinitroaniline herbicides could bind directly behind the α-tubulin N-loop (H1–S2 loop, amino acids 29–64) or close to the L-loop (S9–S10 loop, amino acids 356–373). ,− Meanwhile, other studies have proposed that ORYbs might be located on top of the N-loop near to the β-tubulin interface (see Figure D). − Unfortunately, these proposed binding sites are found in poorly accessible regions, away from amino acids with known OR mutations or comprise several highly conserved residues between ORY-susceptible and non-susceptible organisms.…”