Department of Chemistry, Center for Diagnostics and Therapeutics and Advanced Translational Imaging Facility, Georgia State University, Atlanta, GA 30303, USA.
School of Science and Technology, Georgia Gwinnett College, Lawrenceville, GA 30043, USA.
Molecules. 2020 May 4;25(9):2148. doi: 10.3390/molecules25092148.
Calcium controls numerous biological processes by interacting with different classes of calcium binding proteins (CaBP's), with different affinities, metal selectivities, kinetics, and calcium dependent conformational changes. Due to the diverse coordination chemistry of calcium, and complexity associated with protein folding and binding cooperativity, the rational design of CaBP's was anticipated to present multiple challenges. In this paper we will first discuss applications of statistical analysis of calcium binding sites in proteins and subsequent development of algorithms to predict and identify calcium binding proteins. Next, we report efforts to identify key determinants for calcium binding affinity, cooperativity and calcium dependent conformational changes using grafting and protein design. Finally, we report recent advances in designing protein calcium sensors to capture calcium dynamics in various cellular environments.
钙通过与不同类别的钙结合蛋白（CaBP）相互作用来控制许多生物过程，这些 CaBP 具有不同的亲和力、金属选择性、动力学和钙依赖的构象变化。由于钙的配位化学多样性以及与蛋白质折叠和结合协同性相关的复杂性，预计 CaBP 的合理设计将带来多重挑战。在本文中，我们将首先讨论钙结合位点在蛋白质中的统计分析的应用，以及随后开发的预测和识别钙结合蛋白的算法。接下来，我们报告了使用嫁接和蛋白质设计来确定钙结合亲和力、协同性和钙依赖构象变化的关键决定因素的努力。最后，我们报告了设计蛋白质钙传感器以在各种细胞环境中捕获钙动力学的最新进展。
