ELECTRONIC STRUCTURE CHARACTERIZATION OF PEPTIDE POLYMERS AND ANTIBODY-ANTIGEN COMPLEX.

In biomolecules, the organization of electronic structure depends on chemical composition, structural polarization, and intermolecular interactions, and may influence relevant processes. Although classical molecular modeling approaches enable the investigation of conformational stability, structural dynamics, and noncovalent interactions, electronic structure descriptors provide complementary information on frontier orbitals, charge polarization, electronic delocalization, and electron density sharing between molecular fragments. This work investigated how the chemical identity of residues in model peptide polymers and the formation of biomolecular interfaces modulate electronic organization. A series of CH3–Gly5–X–Gly5–CH3 polymers was analyzed, in which X represented each of the 20 canonical amino acids at the central position. This strategy allowed us to evaluate how substitution by a single amino acid affects the density of electronic states, the HOMO–LUMO gap, frontier orbital localization, and electronic delocalization. Calculations were performed with ORCA 5.0.4 using density functional theory at the B3LYP/6-31G* level. The analysis was extended to the Fab–lysozyme antibody–antigen complex, PDB 1BQL, prepared at physiological pH and evaluated using the GFN2-xTB method. Electron density sharing maps were generated between the antigen Y chain and the antibody H and L chains. The results showed that substitution of the central residue reorganized the electronic structure of the peptide chain. Variation of X altered the HOMO–LUMO gap, the spatial distribution of frontier orbitals, and the degree of electron delocalization. Charged, polar, aromatic, and sulfur containing residues favored orbital localization on the central residue, its side chain, or adjacent regions. Anionic residues introduced occupied states within the region originally corresponding to the energy gap, whereas cationic residues introduced unoccupied states in the same region. These effects resemble band gap narrowing in organic semiconductors and demonstrate how residue chemistry can tune peptide electronic behavior under equivalent structural and computational conditions. In the Fab–lysozyme complex, electron density sharing was heterogeneous and concentrated in regions of the Y, H, and L chains, indicating localized electronic contributions to antibody–antigen recognition. Taken together, the results connect electronic properties observed in model peptide systems with the electronic organization of biomolecular interfaces, providing a complementary physicochemical perspective on polarization, stabilization, and electronic communication in biological systems.