A fast and efficient virtual screening and identification strategy for helix peptide binders based on finDr webserver: A case study of bovine serum albumin (BSA).

Peptides offer unique advantages, including strong specificity, rapid action, and low side effects, making them a prominent focus in the development of new drugs and functional materials. However, the rapid and efficient screening and identification of high-affinity peptides for specific targets remains a significant challenge. In this study, we successfully screened 12-helix candidate peptides using bovine serum albumin (BSA) as the target protein, employing the computer-aided peptide virtual screening webserver finDr. Among the top five candidate peptides, we identified E4-TP2 (GVATVVARLFLL) as the peptide capable of binding BSA with high affinity constant (K = 39.4 nM), confirmed through an in vitro molecular interaction instrument. The interaction mode of the peptide-BSA complex was analyzed using Ligplot software, revealing that the primary interactions involved hydrophobic forces and hydrogen bonds. Additionally, molecular dynamics simulations further elucidated the molecular mechanisms underlying the high-affinity peptide interactions, the results demonstrated that the complex exhibited good conformational stability and strong binding free energy (MM/PBSA: -21.075 ± 5.471 kJ/mol). In conclusion, the finDr virtual screening strategy and the molecular interaction identification method employed in this study provide a robust technical approach for the rapid and efficient acquisition of high-affinity binding peptides for target proteins of interest.