최루성 Capsaicin 유도체의 Vanilloid (TRPV1; PDB 2R9R) 수용체에 대한 분자도킹에 미치는 영향
Influence on the Molecular Docking to Vanilloid Receptor (TRPV1; PDB 2R9R) of Lachrymal Capsaicin Analogs
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초록
매운 맛을 느끼는데 필요한 고통을 통합하고 관리하는 경로의 vanilloid 수용체(TRPV1; PDB2R9R)에 대한 기질 분자로서 최루성 capsaicin 유도체(1-8)의 분자도킹에 미치는 영향을 검토하였다. 수용체 내 반응점은 4 부분(A-D)이 선택되었고 그 중에서 A가 제일 커다란 부피(A; 28Å3)를 보였다. 특히, 기질 분자들은 반응점 A에 대한 도킹 스코어가 가장 큰 경향이었으며 dihydrocapsaicin (2) 분자가 제일 큰 도킹 스코어(DS = 5.36)를 나타내었다. 도킹 스코어(DS)와 capsaicin 유도체의 물리-화학 파라미터사이의 SAR-모델로부터 도킹 스코어에 가장 큰 영향을 미치는 요소는 입체상수로서 R-치환기의 최대 폭(B4)과 Lipole 상수(BL)이었다. 또한, 도킹 스코어와 Lipole 상수의 2차식 포물선 관계로부터 Lipole 상수가 적정값(BLopt .= 21.65)을 나타낼 경우에 가장 큰 도킹 스코어(DSmax.= 4.68)를 나타냄을 알았으며 이 조건에 상응하는 화합물은 가장 매운 맛을 나타내는 capsaicin (1) 분자이었다.
Abstract
A molecular docking study with lachrymal capsaicin analogs (1-8) as substrate molecules was carriedout to the vanilloid receptors (TRPV1; PDB 2R9R) within the pain pathway, which is required for the detectionof heat. The study showed that the 4 active sites pocket (A-D) in the receptor was identified and the volume(A: 28?3) on A was the largest among them. Furthermore, the substrate molecules generated tendency of bestdocking scores when docked to the A pocket. And the dihydrocapsaicin (2) molecule has the biggest dockingscore (DS=5.36) for the active site pocket (A). The Influences on the molecular docking to the vanilloid receptorand the SAR models from the correlationships between docking scores (DS) and various physicochemicalparameters of capsaicin analogs (1-8) were discussed quantitatively. The maximum width (B4) and bond-lipole(BL) constants of R-substituents in capsaicin analogs as steric constant had the greatest effect on increasingthe rate of molecular docking. The capsaicin analogs (1-8) had the best docking score due to the influence of the optimum BL constant (BLopt.=21.65) from the quadratic equation between DS and BL constants. Therefore,it was found that the capsaicin (1) molecule was satisfied with the terms described as the hottest spice pepper.
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