Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, 2-4 Shirakata, Tokai-mura, Naka-gun, Ibaraki 319-1106, Japan; Laboratoire Interdisciplinaire de Physique (LiPhy), Grenoble-Alpes University, 140 rue de la physique, 38402 Saint Martin d'Hères, France; Institut Laue-Langevin, 71 avenue des Martyrs, CS 20156, 38042 Grenoble Cedex 9, France.
Biophys Chem. 2021 May;272:106574. doi: 10.1016/j.bpc.2021.106574. Epub 2021 Mar 9.
To study the effects of the interdomain flexibility on the encounter rate of nucleocapsid-type protein with drug molecules, where two domains (NTD) are connected by a flexible linker and each NTD has a drug binding site, two-dimensional random walk simulation was carried out as a function of the interdomain flexibility and the drug concentration. NTDs represented as circles undergo random motions constrained by the interdomain flexibility while drug molecules are represented by lattice points. It was found that as the interdomain flexibility increases, the time interval between the drug bindings to the 1st and 2nd NTDs decreases, suggesting that the 2nd drug binding is accelerated. Furthermore, this effect was more significant at lower drug concentrations. These results suggest that the interdomain linker plays a key role in the drug binding process and thus emphasize the importance of characterization of their physicochemical properties to better evaluate the efficacy of potential drugs.
为了研究结构域间柔性对核衣壳型蛋白与药物分子结合频率的影响，其中两个结构域（NTD）由一个柔性接头连接，每个 NTD 都有一个药物结合位点，我们进行了二维随机漫步模拟，模拟的函数包括结构域间柔性和药物浓度。NTD 用圆圈表示，它们在结构域间柔性的约束下进行随机运动，而药物分子则用晶格点表示。结果发现，随着结构域间柔性的增加，药物结合到第一个和第二个 NTD 的时间间隔减小，这表明第二个药物结合被加速。此外，在较低的药物浓度下，这种效应更为显著。这些结果表明，结构域间接头在药物结合过程中起着关键作用，因此强调了对其理化性质进行特征描述的重要性，以便更好地评估潜在药物的疗效。
