Significance: Density functionals with Hartree–Fock exchange have been widely used for a wide range of chemical applications, but the nonlocal character of exchange makes long-range exchange computationally expensive for solid-state calculations with periodic boundary conditions, and full exchange is nonphysical for condensed-phase systems. Here, we present a screened-exchange (SX) density functional, M06-SX, that is especially designed to have good accuracy for both solid-state physics and chemical applications with less computational cost than full Hartree–Fock exchange. The M06-SX functional gives accuracy comparable to functionals with full Hartree–Fock exchange for predicting chemical properties of molecules, while also being practical with good accuracy for plane wave calculations on band gaps and lattice constants of solids.

Food‐derived angiotensin I‐converting enzyme (ACE) inhibitory peptides represent a potential source of new antihypertensive. However, their characteristics and binding mechanisms were not well understood. In this study, novel energy calculation and experimentation were combined to elucidate the characteristics and mechanisms of ACE inhibitory tripeptides. ACE inhibitory activity of all 8,000 tripeptides was investigated by in silico experiments. IC₅₀ values of the five top‐rated tripeptides ranged from 5.86 to 21.84 μM. Five hundred top‐ranked tripeptides were chosen for detailed structure–activity analysis, and a significant preference for aromatic amino acids at both C‐ and N‐terminus was found. By binding free energy analysis of nine representative tripeptides via MM/GBSA, electrostatic energy was found to be the leading energy that contributed to the binding of ACE with its high affinity tripeptides. Besides, S355, V380, and V518, three residues positioned around the classical binding pockets of ACE, also played a key role in ACE's binding. Therefore, for tripeptides, their binding pockets in ACE were redefined. In conclusion, the characteristics of ACE inhibitory peptides were more deeply illustrated by the thorough analysis of all tripeptides. The energy analysis allows a better understanding of the binding mechanisms of ACE inhibitory peptides, which could be used to redesign the ACE inhibitors for stronger inhibitory activity.