Virtual Screening of Soybean Protein Isolate-Binding Phytochemicals and Interaction Characterization

Soybean protein isolate (SPI) and small molecule interactions have drawn more and more attention regarding their benefits for both parts, while research on large-scale investigations and comparisons of different compounds is absent. In this study, a high throughput virtual screening was applied on a phytochemical database with 1130 compounds to pinpoint the potential SPI binder. Pentagalloylglucose, narcissoside, poliumoside, isoginkgetin, and avicurin were selected as the top-five ranking molecules for further validation. Fluorescence quenching assays illustrated that isoginkgetin has a significantly higher apparent binding constant (Ka) of (0.060 ± 0.020) × 10(6) L·mol(−1), followed by avicularin ((0.058 ± 0.010) × 10(6) L·mol(−1)), pentagalloylglucose ((0.049 ± 0.010) × 10(6) L·mol(−1)), narcissoside ((0.0013 ± 0.0004) × 10(6) L·mol(−1)), and poliumoside ((0.0012 ± 0.0006) × 10(6) L·mol(−1)). Interface characterization by MD simulation showed that protein residues E172, H173, G202, and V204 are highly involved in hydrogen bonding with the two carbonyl oxygens of isoginketin, which could be the crucial events in SPI binding. Van der Waals force was identified as the major driven force for isoginketin binding. Our study explored SPI–phytochemical interaction through multiple strategies, revealing the molecular binding details of isoginkgetin as a novel SPI binder, which has important implications for the utilization of the SPI–phytochemical complex in food applications.