Screening Peptide Binders to IL-17A Using Classical Molecular Dynamics
- 1ShenZhen UnibindMD Computation Biotech Co., Ltd.
Abstract
Identifying short peptides that bind therapeutically relevant proteins is a practical step toward developing peptide-based inhibitors. Here we screened 64 tetrapeptides for binding to the IL-17A homodimer using classical all-atom molecular dynamics simulations (GROMACS 2022.2, FF19SB force field, TIP3P water, 200 ns production per complex). Binding was ranked by a composite score that combines short-range interaction energies (Coul-SR + LJ-SR), close-contact frequency, mean intermolecular distance, and hydrogen bond occupancy. The tetrapeptide LYS-THR-CYS-ASP achieved the highest score in the set (composite score 2.85, total interaction energy -556 kJ/mol, average 8.0 H-bonds). Across all 64 simulations, electrostatic interactions accounted for approximately 72% of the total interaction energy. Stronger binders tended to contain charged and polar residues (Asp, Glu, Cys, Arg, Thr), while weaker binders were enriched in hydrophobic residues. Contact analysis identified a recurring interaction surface on IL-17A centered on cysteine and aromatic residues (Chain A: CYS87, Chain B:CYS196, A:HIS86, B:TYR175, B:HIS195), which we describe as a cysteine-aromatic cradle. These results nominate LYS-THR-CYS-ASP as a candidate for experimental binding validation and suggest simple sequence guidelines for designing IL-17A-targeting peptides.
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BibTeX
@misc{xu2026screening,
title = {{Screening Peptide Binders to IL-17A Using Classical Molecular Dynamics}},
author = {W. Xu and W. Fu},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749315},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749315v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Screening Peptide Binders to IL-17A Using Classical Molecular Dynamics
AU - W. Xu
AU - W. Fu
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749315
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749315v1
AB - Identifying short peptides that bind therapeutically relevant proteins is a practical step toward developing peptide-based inhibitors. Here we screened 64 tetrapeptides for binding to the IL-17A homodimer using classical all-atom molecular dynamics simulations (GROMACS 2022.2, FF19SB force field, TIP3P water, 200 ns production per complex). Binding was ranked by a composite score that combines short-range interaction energies (Coul-SR + LJ-SR), close-contact frequency, mean intermolecular distance, and hydrogen bond occupancy. The tetrapeptide LYS-THR-CYS-ASP achieved the highest score in the set (composite score 2.85, total interaction energy -556 kJ/mol, average 8.0 H-bonds). Across all 64 simulations, electrostatic interactions accounted for approximately 72% of the total interaction energy. Stronger binders tended to contain charged and polar residues (Asp, Glu, Cys, Arg, Thr), while weaker binders were enriched in hydrophobic residues. Contact analysis identified a recurring interaction surface on IL-17A centered on cysteine and aromatic residues (Chain A: CYS87, Chain B:CYS196, A:HIS86, B:TYR175, B:HIS195), which we describe as a cysteine-aromatic cradle. These results nominate LYS-THR-CYS-ASP as a candidate for experimental binding validation and suggest simple sequence guidelines for designing IL-17A-targeting peptides.
ER -