食品科学2024，Vol.45Issue(17)：52-62,11.DOI:10.7506/spkx1002-6630-20240204-011
基于分子对接及动力学模拟的红曲橘霉素合成小分子抑制剂的高通量筛选
High Throughput Screening of Small Molecule Inhibitors for the Synthesis of Red Yeast Citrinin Based on Molecular Docking and Dynamic Simulation
摘要
Abstract
This study investigated high-throughput screening of inhibitors for the key enzyme CitE in the synthesis of red yeast citrinin through computer simulation.First,Alphafold 2 was used to build the homology model of CitE.and it was aligned with similar sequences to predict the ligand binding region.Subsequently,a ligand library of 20 000 compounds was constructed by searching for natural ligands and flavonoid skeleton analogues in the Arthur database.Afterwards,molecular docking of the CitE protein to the library of small molecule compounds was performed using Maestro to select potential CitE ligands.Gromacs kinetic simulation was used to evaluate the binding stability,and the binding free energy was calculated using MM/PBSA.The protein-ligand binding mode was analyzed,confirming that six small molecule ligands including quercetin,luteolin,apigenin,genistein,5,4'-dihydroxyflavone,and fisetin had strong CitE binding activities.The results from solid and liquid state fermentation showed that the above compounds exhibited significant inhibitory activity against Monascus citrinin production.Specifically,the addition of these compounds in solid state fermentation(20 mg/28 g of dry material)resulted in a reduction of Monascus citrinin production by 42.52％,48.81％,32.54％,32.57％,21.02％,and 13.67％,respectively,while their addition in liquid state fermentation(0.1 g/L)led to a reduction by 33.77％,15.58％,33.33％,62.34％,58.87％,and 50.22％,respectively.In summary,this study is of reference significance for establishing an efficient and safe Monasucs fermentation system.关键词
红曲霉/橘霉素/抑制剂/分子对接/分子动力学模拟/CitEKey words
Monascus/citrinin/inhibitors/molecular docking/molecular dynamics simulation/CitE分类
轻工业引用本文复制引用
李居行,葛佳琦,张志宇,何苗,崔萌菲,郭庆彬,李贞景,王昌禄,刘欢欢..基于分子对接及动力学模拟的红曲橘霉素合成小分子抑制剂的高通量筛选[J].食品科学,2024,45(17):52-62,11.基金项目
国家自然科学基金面上项目(32272277) （32272277）
