Lešnik Samo, Jukič Marko, Bren Urban
Laboratory of Physical Chemistry and Chemical Thermodynamics, Faculty of Chemistry and Chemical Engineering, University of Maribor, Smetanova ulica 17, SI-2000 Maribor, Slovenia.
IOS, Institute of Environmental Protection and Sensors, Beloruska ulica 7, SI-2000 Maribor, Slovenia.
Foods. 2023 Jan 14;12(2):408. doi: 10.3390/foods12020408.
Rosemary represents an important medicinal plant that has been attributed with various health-promoting properties, especially antioxidative, anti-inflammatory, and anticarcinogenic activities. Carnosic acid, carnosol, and rosmanol, as well as the phenolic acid ester rosmarinic acid, are the main compounds responsible for these actions. In our earlier research, we carried out an inverse molecular docking at the proteome scale to determine possible protein targets of the mentioned compounds. Here, we subjected the previously identified ligand-protein complexes with HIV-1 protease, K-RAS, and factor X to molecular dynamics simulations coupled with free-energy calculations. We observed that carnosic acid and rosmanol act as viable binders of the HIV-1 protease. In addition, carnosol represents a potential binder of the oncogene protein K-RAS. On the other hand, rosmarinic acid was characterized as a weak binder of factor X. We also emphasized the importance of water-mediated hydrogen-bond networks in stabilizing the binding conformation of the studied polyphenols, as well as in mechanistically explaining their promiscuous nature.
迷迭香是一种重要的药用植物，具有多种促进健康的特性，尤其是抗氧化、抗炎和抗癌活性。鼠尾草酸、鼠尾草酚和迷迭香醇，以及酚酸酯迷迭香酸，是导致这些作用的主要化合物。在我们早期的研究中，我们在蛋白质组规模上进行了反向分子对接，以确定上述化合物可能的蛋白质靶点。在此，我们对先前鉴定的与HIV-1蛋白酶、K-RAS和因子X的配体-蛋白质复合物进行了分子动力学模拟，并结合自由能计算。我们观察到鼠尾草酸和迷迭香醇是HIV-1蛋白酶的可行结合剂。此外，鼠尾草酚是癌基因蛋白K-RAS的潜在结合剂。另一方面，迷迭香酸被表征为因子X的弱结合剂。我们还强调了水介导的氢键网络在稳定所研究多酚的结合构象以及从机制上解释它们的混杂性质方面的重要性。
