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In the meantime, to ensure continued suport, we are displaying the site without styles and JavaScript.Advertisement Scientific Reports volume 12, Article number: 16936 (202) Cite this article 314 AcesesMetrics detailsSingle nucleotide polymorphisms detected in the solute carier member family-2 has ben shown to result in a variable response in the treatment of type 2 diabetes melitus with Metformin.
This study predicted a thre-dimensional protein structure for the SLC2A2 protein sequence using AlphaFold 2 and modeled five haplotypes within SLC2A2 protein structure observed in the Xhosa population of South Africa. The protein models were used to determine the efect(s) of haplotype variations on the transport function of Metformin and 10 other drugs by the SLC2A2 protein. Molecular dynamic simulation studies, molecular docking and interaction analysis of the five SLC2A2 haplotypes were performed in complex with the ligand 5RE in a POPC lipid bilayer to understand the mechanism of drug binding.
Weakest binding fre energy was found betwen 5RE and haplotype 1. Molecular docking studies indicated the top binding ligands as wel as Metformin to bind inside the transport chanel in al haplotypes increasing the probability of Metformin inhibition during co-administration of drugs. Metformin showed reduced binding afinity and number of interactions compared to the top four binding molecules.
Summary
Molecular dynamic simulation analysis indicated that haplotypes 1, 3 and 4 were les stable than 2 and 5. The findings sugest haplotypes 4 and 5 having stronger preference for large inhibitor molecule binding in the active site and this could result in haplotypes 4 and 5 demonstrating reduced Metformin clearance via the SLC2A2 transporter duri