Engineering a Transmitter Binding Site

设计发射器绑定位点

基本信息

批准号：
9270608
负责人：
Anthony L Auerbach
金额：
$ 48.43万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9270608
关键词：
Address Affinity Agonist Amino Acids Behavior Binding Binding Sites Biological Assay Biological Models Cell membrane Cell physiology Cells Cholinergic Receptors Complementary DNA Complex Couples Coupling Disease Drug Targeting Electrophysiology (science)Energy-Generating Resources Engineering Equilibrium Event Free Energy Global Change Goals Health Human Hydrogen Bonding Ions Kinetics Knowledge Ligand Binding Ligands Measurement Measures Mechanics Membrane Proteins Molecular Molecular Conformation Molecular Machines Movement Mutation Nature Nicotinic Receptors Output Pharmaceutical Preparations Pharmacology Physiology Play Power Sources Probability Process Protein Conformation Proteins Resolution Roentgen Rays Role Shapes Site Solvents Source Structure Therapeutic Translating Vertebral column Work cost design experimental study logarithm nervous system disorder neuromuscular operation patch clamp public health relevance receptor response

项目摘要

DESCRIPTION (provided by applicant): A fundamental principle of biomedicine is that drugs bind to proteins to influence their output and, hence, cell physiology. The overall goal of our experiments is to understand the mechanisms by which ligands bind to neuromuscular acetylcholine receptors, and how this event influences the probability that these membrane proteins allow ions to cross the cell membrane. These receptors are molecular machines that reversibly couple the energy of ligand binding to that for the mechanical work of a global conformational change. Our objective is to reveal the moving parts of the binding site apparatus, and to measure the energy changes associated with each part. By doing so we will understand, design and control how this receptor responds to drugs. This knowledge can be applied to closely-related receptors that are common targets for drugs (both therapeutic and of abuse) and play roles in behavior and diseases of the nervous system.

描述（由申请人提供）：生物医学的基本原理是药物与蛋白质结合以影响其输出，从而影响细胞生理学。我们实验的总体目标是了解配体与神经肌肉乙酰胆碱受体结合的机制，以及该事件如何影响这些膜蛋白允许离子穿过细胞膜的概率。这些受体是分子机器，可将配体结合的能量可逆地耦合到整体构象变化的机械功。我们的目标是揭示结合位点装置的运动部件，并测量与每个部件相关的能量变化。通过这样做，我们将了解、设计和控制这种受体如何对药物做出反应。这些知识可以应用于密切相关的受体，这些受体是药物（治疗和滥用）的共同目标，并在神经系统的行为和疾病中发挥作用。