关键词: ACE抑制肽, 血管紧张素转化酶, 分子模拟

Abstract: An investigation into the molecular mechanisms of interaction between angiotensinⅠ-converting enzyme (ACE) and each of four typical ACE-inhibitory peptides derived from milk proteins, KVLPVP (Lys-Val-Leu-Pro-Val-Pro), YKVPQL (Tyr-Lys-Val-Pro-Gln-Leu), VYPFPG (Val-Tyr-Pro-Phe-Pro-Gly), and IASGQP (Ile-Ala-Ser-Gly-Gln-Pro) was carried out using the flexible molecule docking technology to determine the action sites, types of intermolecular force and interaction energy between them. It was shown that hydrogen bond, hydrophobic, hydrophilic and electrostatic interactions and coordinate bond (Zn2+) existed between the active pockets of ACE and each of the studied ACE-inhibitory peptides, which were together responsible for maintaining the conformational stability of the complexes. The key amino acid residues in the active pockets were His 353, Ala 354, Ser 355, Ala 356, Glu 384, Glu 411, Pro 519, Arg 522 and Tyr 523 and the key groups in the small peptides N-terminal amino groups, carbonyl groups of peptide bonds, C-terminal carboxyl groups. The ACE-inhibitory peptides could be ranked in increasing order of interaction energy between ACE and each of them as follows: KVLPVP, YKVPQL, VYPFPG, and IASGQP. As a consequence, their binding with ACE decreased and the IC50 values increased in the same order.

Key words: ACE-inhibitory peptides, angiotensin Ⅰ-converting enzyme, molecular modeling