The affinity of PLP-1 protein and vitamins (Vb6/Vb12) by molecular docking

Description:

PLP1 does not have a publicly available crystal structure, so the model predicted by Alphafold3 is used as a template for docking. In this study, we employed a semi flexible docking method. Firstly, we downloaded the crystal structure of the target protein PLP-1 from a protein database or modeled it using AlphaFold3. Then, we used Maestro computational software to prepare the structures of proteins and small molecules separately. During the protein preparation process, optimize the hydrogen bond network and minimize the energy of the protein system. Small molecule preparation: Generate three-dimensional structures and minimize energy, and generate multiple conformations (15) to increase the likelihood and accuracy of successful docking. Next, we use the sitemap module of Maestro software to predict the binding pocket of small molecules (default parameters) and generate a receiver grid file. Based on the predicted pocket location, size, and small molecule docking score, we determine the most likely binding pocket. The other parameters remained at their default values. During molecular docking, select the prepared grid file and small molecules in the small molecule docking ligand docking module for molecular docking. Based on the scoring of docking results and the rationality of small molecule binding conformation, the optimal binding mode is selected through comprehensive analysis and judgment. The docking results were visualized using Pymol software. Vb6 combining pattern analysis: VB6 molecules occupy hydrophobic pockets composed of LEU86, PHE257, THE93, and ALA17. The pyridine nitrogen of Vb6 interacts with the hydroxyl group of SER18 through hydrogen bonding, the phenolic hydroxyl group of VB6 interacts with the hydroxyl group of THR93 through hydrogen bonding, and the phosphate group interacts with the amino group of ALA17 SER18 through hydrogen bonding. Vb12 combined with pattern analysis: Vb12 molecules occupy a larger hydrophobic pocket composed of ALA260, TYR263, LEU11, VAL12, PRO15, and PHE16. The phosphate group of Vb12 forms hydrogen bonds with the amide side chain of ASN264.