INTERACTIONS OF GENERAL ANESTHETICS WITH CALCIUM BINDING CALMODULIN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 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 描述所用计算方法的关键词：分子动力学模拟，自由能计算 翻译后摘要：本分配的目的是进行计算模型的影响，全身麻醉药的结构和功能 钙结合蛋白钙调素的动力学。将在存在和不存在吸入麻醉剂氟烷的情况下评价钙与钙调蛋白的结合亲和力。要使用的计算技术涉及运行所有原子分子动力学模拟，并通过来自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最小，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。这项研究将提供有关麻醉剂对蛋白质作用的基本机制的知识，包括（1） 在麻醉剂存在下蛋白质配体的天然亲和力的变化;（2）蛋白质中麻醉剂结合位点的鉴定;和（3）麻醉剂与蛋白质动力学结合的结果和天然构象的稳定性。结果将显着有助于了解麻醉剂结合到一个 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.