Human angiotensin-converting enzyme (ACE) is a well-established druggable target for the treatment of hypertension (HTN), which contains two structurally homologous but functionally distinct N-and C-domains. Selective inhibition of the C-domain primarily contributes to the antihypertensive efficiency and can be exploited as medicinal agents and functional additives for regulating blood pressure with high safety. In this study, we used a machine annealing (MA) strategy to guide the navigation of antihypertensive peptides (AHPs) in structurally interacting diversity space with the two ACE domains based on their crystal/modeled complex structures and an in-house protein-peptide affinity scoring function, aiming to optimize the peptide selectivity for C-domain over N-domain. The strategy generated a panel of theoretically designed AHP hits with a satisfactory C-over-N (C > N) selectivity profile, from which several hits were found to have a good C > N selectivity, which is roughly comparable with or even better than the BPPb, a natural C > N-selective ACEinhibitory peptide. Structural analysis and comparison of domain-peptide noncovalent interaction patterns revealed that (i) longer peptides (>4 amino aids) generally exhibit stronger selectivity than shorter peptides (<4 amino aids), (ii) peptide sequence can be divided into two, section I (including peptide C-terminal region) and section II (including peptide middle and N-terminal regions); the former contributes to both peptide affinity (primarily) and selectivity (secondarily), while the latter is almost only responsible for peptide selectivity, and (iii) charged/polar amino acids confer to peptide selectivity relative to hydrophobic/nonpolar amino acids (that confer to peptide affinity).

Although slippery liquid‐infused porous surfaces (SLIPSs) have been extensively studied for anticorrosion and antifouling applications, their durability and stability restrict their practicality. Herein, a technique is presented for fabricating SLIPS with dual‐protection. First, a polydimethylsiloxane (PDMS) coating with a pyramidal morphology is fabricated through mold‐based lithographic techniques. The mold is prepared by applying a texturing process to a monocrystalline silicon wafer of the type used to produce solar cells. Once infused with lubricant, the SLIPS is prepared and has a water‐contact angle of 112°, on an inclined surface, water droplets slide easily off its surface. Due to the excellent chemical stability and low superficiality of the lubricant layer, the SLIPS offers excellent antifouling and anticorrosion properties. In a static marine environment, the SLIPS has an extremely low coverage fraction of algae. After being immersed in a 3.5% NaCl solution for 400 days, |Z|0.01 Hz ≈ 1011 Ω, and the phase angle at high frequency is approximately −90°. SLIPSs based on the PDMS coating provide dual protection (anticorrosion and antifouling), showing that this design approach produces SLIPSs with excellent potential for applications in marine environments.