Investigation of interactions between subunits of polypeptides and nucleic acids (monomeric-tetrameric) by molecular modelling

Transcription factors (TF) are proteins which are consisted of combinations of many different amino acids. The amino acid sequences in the structure provide three-dimensional structure due to the entalpy value of the external environment and the non-covalent interactions. A protein must be in its optimal 3D conformational structure to perform its function: effectively binding to DNA. In this study, the non-covalent interactions between AG and CC nucleotide dimer sequences in the single-stranded DNA, known to be effectively bound to REST, and the triple serine structure of the DNA binding region of RE-1 (Suppressor Element-1) silencer transcription factor (REST) were investigated by computational molecular methods. For this purpose, Spartan 14 program was used to find triple serine molecule structures and nucleotide dimer structures by conformational analysis. The MOPAC program with PM6-D3H4 method and Gaussian09 program with B3LYP-6-311++G(d,p) level were used for optimizations (opt) and frequency (freq) calculations for each investigated conformer. Using the calculated results, the most stable structures were determined using the relative energies. Molecular structures were drawn by Discovery Studio Visualizer 2019. As a result, it was found that serine residues in the active DNA binding region of REST protein can form hydrogen (–H) bonds with DNA. Other non-covalent interactions such as van der Walls forces were not identified.