## 1 Introduction  
As one of the most common chronic diseases, hypertension is associated with many other diseases such as cardiovascular diseases, arteriosclerosis, and stroke. Now, it is estimated that the total number of worldwide hypertension patients is approximately 1 billion and will increase to more than 1.6 billion by 2025 [1], and it kills 9 million people annually [2].  
Angiotensin I-converting enzyme (ACE) is a crucial enzyme in regulating blood pressure, as it can transform angiotensin I to angiotensin II in the human renin-angiotensin system and also convert vasodilator bradykinin into an inactive peptide via kallikrein-kinin systems [3]. Therefore, ACE is demonstrated as a potential target for antihypertensive agents. Currently, synthetic ACE inhibitors, including captorpil, benzoepit, canalapril, and peridopril, are associated with various side effects, such as coughing, taste disturbance, allergic reactions, and skin rashes [4]. This raises the need to find more ACE inhibitors with less adverse effects for hypertension management [5].  
Food-derived ACE inhibitors have become popular in hypertension management due to their fewer number of adverse effects. A number of ACE inhibitory peptides have been detected from marine sources, such as algae protein [6], sadine protein [7], cod skin gelatin [8], salmon byproduct protein [9], and sea cucumbers [10]. However, shellfish-derived ACE inhibitory peptides have been rarely reported, although a few examples are available, such as cyclina sinensis protein [11] and pear oyster protein [12].  
It is noted that the entire process of isolating ACE inhibitory peptides from natural proteins by conventional methods is cumbersome and time consuming. Generally, several steps are involved, such as membrane separation, ion exchange chromatography, gel permeation chromatography, and high-performance liquid chromatography, which greatly complicates the preparation process and increases the cost [13]. Alternatively, computer-aided prediction and identification of food-protein-derived bioactive peptides has become a feasible method [14]. Compared with traditional experimental studies, in silico analyses are time saving and more economical to quickly discover novel ACE inhibitory peptides. For example, [PERSON] et al. [15] used in silico proteolysis to identify ACE inhibitory peptides from bovine collagen, and the most active one was identified as a pentapeptide (Gly-Pro-Arg-Gly-Phe). Similarly, an in silico analysis was carried out to predict the likelihood of obtaining ACE inhibitory peptides from oat protein hydrolysates, and nine peptides (FFG, IFFFL, PFL, WWK, WCY, FPIL, CPA, FLLA, and FEPL) were found to inhibit ACE by between 86.5 \(\pm\) 10.7% and 96.5 \(\pm\) 25.8% [16].  
More importantly, proteins will be degraded to amino acids or peptides after gastrointestinal consumption; hence, the nutritional value of protein supplements is dependent on the released peptides after degradation in the gastrointestinal tract. To keep the released peptides active after ingestion, they have to be resistant to gastrointestinal degradation [17]. The goal of this study is to identify shellfish-derived proteins and peptides to be supplemented in the diet of hypertensive patients, which is expected to help lower blood pressure. Specifically, in silico gastrointestinal proteolysis was performed on marine shellfish proteins, producing a large number of peptides. Additionally, the binding abilities of these peptides to the key target ACE were then computationally accessed, whereas the in vitro ACE inhibitory activities of the identified peptides were further confirmed by experimental results. Thus, proteins with a high content of ACE-binding peptides are expected to provide nutritional support for hypertensive patients. In particular, the identified peptides with a high binding ability to ACE can serve as the leading compounds in the development of ACE inhibitors.