Paper Title
Small Oligopeptides as Specific Potential Inhibitors for Arabidopsis Group A Protein Phosphatases Type 2c

In Arabidopsis, Group AProtein Phosphatases type 2C (PP2C) acts as an important regulators and effectors of the Abscisic acid pathway (ABA). The current knowledge about the catalytic mechanism of PP2Cs inactivation simplifythe development of group A PP2C inhibitors. In our approach, we used modern Bioinformatics and Computational Chemistry methods to identify small oligopeptides with potential inhibitory effect on PP2Cs group A. Screening of new combinatorial library of small oligopeptides was performed to identify new ABI1 PP2C inhibitors. Certain sequence of oligopeptides including few amino acid residues are crucial for the specificity of ABI1-PYL1 and ABI1-SnRK2.6 interactions. The combinatorial library consistsof 4 to 5 amino acid long oligopeptides without repetition in different forms: linear peptide,head-to-tail cyclic peptides and disulfide-constrained cyclic peptides. Each structure of oligopeptide compound was optimized and dockingwas performed. Over twenty thousand compounds for virtual screening studies were accessed, followed by Molecular Docking, Scoring functions and MM-GBSA analysis to evaluate the results. The lead structure of each screening trails were used to generate new pharmacophore models that will enable to rescreenthe library to find new potential inhibitors or to generate de novo ligands.Virtual screening procedure identified three chemical compounds with high levels of each scoring functions. The precision of the calculations was increased by Quantum chemistry and Molecular mechanics mainly to quantify the binding energy of ligand-protein complex. After the computational optimization of the ABI1-putative inhibitor interaction, new putative inhibitors can be validated in vitro using non-radioactive phosphatase assay. Resulting data allow identification of putative PP2C group A inhibitors that can be used in agriculture. This work has been supported by the Polish National Science Centre grant No. 2016/22/E/NZ3/00345.