Molecular Docking Study of Folic Acid Interaction with Pregnancy-Related Proteins: Implications for Maternal and Fetal Health

Abstract

Folic acid (vitamin B9) is a crucial micronutrient for DNA synthesis, methylation, and amino acid metabolism, playing a vital role in maternal and fetal health. This study investigates the molecular interaction of folic acid with the human reduced folate carrier (RFC, PDB ID: 8DEP) using molecular docking and Density Functional Theory (DFT). Docking results revealed a strong binding affinity (−8.6 kcal/mol) within the RFC binding cavity, stabilized by hydrogen bonds and hydrophobic interactions with key residues including Ser135, Tyr281, Lys353, Phe129, and Leu284. DFT analysis indicated a moderate HOMO–LUMO gap (2.725 eV), high ionization potential (8.496 eV), and a notable electrophilicity index (18.67 eV), reflecting a balanced electronic configuration that supports stable yet reactive interactions. These electronic properties facilitate favorable binding with nucleophilic residues, consistent with docking results. Together, the findings provide a detailed atomic-level understanding of folic acid recognition and transport by RFC, highlighting its mechanistic role in maternal–fetal health and providing a computational basis for future nutritional or therapeutic strategies to prevent pregnancy-related complications.