División de Estudios de Posgrado, Facultad de Química, Universidad Autónoma de Querétaro, Santiago de Querétaro, México.
Dirección de Nuevos Desarrollos, Landsteiner Scientific, Parque Industrial, Toluca, Mexico.
Chem Biol Drug Des. 2019 Jan;93(1):38-49. doi: 10.1111/cbdd.13376. Epub 2018 Nov 25.
Calpains are cysteine proteases involved in the development of several human chronic illnesses such as neurodegenerative diseases, cardiovascular ailments, diabetes, and obesity which constitutes them into possible therapeutic targets. Here, using molecular dynamic simulations and docking, we studied the binding of known inhibitors to representative members of classical and nonclassical calpains. Our aim is to gain better understanding on the inhibition mechanism of calpains and to develop better and more specific inhibitors. Our atomistic models confirmed the importance of calcium ions for the structure of calpains and, as a consequence, their functionality. With these models and their subsequent use in molecular docking, essential structural requirements were identified for the binding of ligands to the calpain catalytic site that provide useful information for the design of new selective calpain inhibitors.
钙蛋白酶是一种半胱氨酸蛋白酶，参与多种人类慢性疾病的发展，如神经退行性疾病、心血管疾病、糖尿病和肥胖症，这使它们成为潜在的治疗靶点。在这里，我们使用分子动力学模拟和对接研究了已知抑制剂与经典和非经典钙蛋白酶代表成员的结合。我们的目的是更好地了解钙蛋白酶的抑制机制，并开发更好、更特异的抑制剂。我们的原子模型证实了钙离子对钙蛋白酶结构及其功能的重要性。利用这些模型及其随后在分子对接中的应用，确定了配体与钙蛋白酶催化位点结合的基本结构要求，为设计新的选择性钙蛋白酶抑制剂提供了有用的信息。
