Prospecting of Novel Angiotensin I-Converting Enzyme Inhibitory Peptides from Bone Collagen of Pelodiscus sinensis by Computer-Aided Screening, Molecular Docking, and Network Pharmacology

Hypertension is a globally prevalent chronic cardiovascular disease, with angiotensin-converting enzyme (ACE) serving as a key target for therapeutic intervention. Synthetic ACE inhibitors have side effects, making natural food-derived ACE-inhibitory peptides a research hotspot owing to safety advantages. Softshell turtle (Pelodiscus sinensis) bone collagen (STBC) has potential bioactivity, but its ACE-inhibitory peptides have not been systematically investigated. This study used computer-aided screening: STBC α1(I) (K7FHL1) and α2(I) (K7G8R1) sequences from UniProt were processed via SignalP 5.0. BIOPEP-UWM analysis showed ACE-inhibitory peptide frequencies of 0.8947 and 0.9261 in the two chains, confirming STBC as a high-quality precursor. Papain-ficin was selected as the optimal enzymatic system via simulation; 105 potential novel peptides were obtained after toxicity/allergenicity prediction. Twenty-seven highly active peptide fragments were screened out via pLM4ACE, and four peptide fragments with relatively high binding energy (QICVCDS, DVWK, IIEY, APMDVG) were identified through molecular docking. These peptides (molecular weight: 536.6–766.9 Da) possessed excellent physicochemical properties and pharmacokinetic characteristics, while bioinformatics analysis revealed that they could target and regulate SRC/HSP90AA1 to modulate the renin-angiotensin system (RAS). This study provides an efficient strategy for the high-value utilization of softshell turtle resources and the development of food-derived ACE-inhibitory peptides.