Molecular modelling of Pro-Gly glyproline and its complexes

In the present work, Pro-Gly glyproline and its biologically active complexes with heparin and with the antithrombin-heparin protein complex have been studied using molecular modelling methods. This molecule is used as a drug and exhibits antithrombotic, anticoagulant immunomodulatory, antiulcer, and antidiabetic effects. The conformational profiles of the dipeptide were studied within the molecular mechanics framework, the geometry and energy of intra- and interresidual interactions were estimated for the most stable states of the investigated dipeptide. A comparative analysis of the extended and folded structures of this molecule optimized by the DFT/B3LYP/6-31+G(d,p) method was carried out, the frontier molecular orbitals were calculated, the surface of the molecular electrostatic potential was studied, the effective charges on the atoms were determined, and the dipole moment and polarizability values were calculated. Molecular docking revealed that the folded structure of Pro-Gly glyproline showed a higher affinity value for both heparin and the antithrombin-heparin protein complex. A model of the pharmacophore of the Pro-Gly molecule for its interaction with a specific receptor was proposed. The obtained data form the basis for the development of effective analogs of glyprolines in the complex with heparin, which are more specific concerning their putative target — antithrombin.