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.