INTERACTIONS OF GENERAL ANESTHETICS WITH CALCIUM BINDING CALMODULIN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 描述研究内容的关键词： 麻醉剂结合、钙亲和力、蛋白质动力学、自由能 描述使用的计算方法的关键词：分子动力学模拟、自由能计算 摘要：本次分配的目的是对全身麻醉药对结构和功能的影响进行计算机模拟。 钙结合蛋白钙调蛋白的动态变化。在吸入麻醉剂氟烷存在和不存在的情况下，将评估钙与钙调蛋白的结合亲和力。要使用的计算技术包括运行所有原子分子动力学模拟，并通过模拟的分子缔合来评估自由能的变化。 结果。初步结果表明，麻醉剂对蛋白质稳定性的影响很小，但能够增强蛋白质的灵活性；这种性质的变化可能会导致对功能的影响以及变化。 对天然配体的亲和力。这项研究将为了解麻醉剂对蛋白质作用的基本机制提供知识，包括(1) 麻醉剂存在时蛋白质配体的天然亲和力的变化；(2)识别蛋白质中的麻醉剂结合部位；(3)麻醉剂结合对蛋白质动力学和天然构象稳定性的影响。研究结果将大大有助于理解麻醉剂与麻醉剂结合的性质和后果 蛋白质靶标。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Keywords to describe research content: anesthetic binding, calcium affinity, protein dynamics, free energy Keywords to descrive computational methods used: Molecular Dynamics simulations, free energy calculations Abstract: The aim of this allocation is to carry out computational modeling of the effect of general anesthetics on structural and functional dynamics of the calcium binding protein calmodulin. The binding affinity of calcium to calmodulin will be evaluated in the presence and absence of the inhaled anesthetic halothane. The computational techniques to be used involve running all atom molecular dynamics simulations and evaluating changes in free energy through molecular associations from the simulated results. Preliminary results suggest that anesthetic have minimal effects on protein stability but are able to enhance protein flexibility; changes of this nature could lead to effects on functionality as well as changes in affinity for natural ligands. The study will provide knowledge into the basic mechanism of anesthetic action on proteins, including (1) the changes in natural affinity for protein ligands in the presence of anesthetics; (2) identification of anesthetic binding sites in proteins; and (3) consequences of the anesthetic binding to the protein dynamics and stability of native conformation. Results will significantly contribute to an understanding of the nature and consequences of anesthetic binding to a protein target.