INTERACTIONS OF GENERAL ANESTHETICS WITH CALCIUM BINDING CALMODULIN

全身麻醉药与钙结合钙调蛋白的相互作用

• 批准号: 7601398
• 负责人: MICHAEL YONKUNAS
• 金额: $ 0.03万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601398
• 关键词: Affinity; Anesthetics; Binding; Binding Sites; Breathing; Calcium; Calcium Binding; Calcium-Binding Proteins; Calmodulin; Computational Technique; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Computing Methodologies; Free Energy; Funding; General anesthetic drugs; Grant; Halothane; Institution; Knowledge; Lead; Ligands; Molecular; Molecular Conformation; Nature; Pliability; Protein Dynamics; Proteins; Research; Research Personnel; Resources; Running; Simulate; Source; United States National Institutes of Health; abstracting; molecular dynamics

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.

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