Engineering a Transmitter Binding Site

描述（由申请人提供）：生物医学的一个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，以及这一事件如何影响这些膜蛋白允许离子穿过细胞膜的可能性。这些受体是分子机器，它们可逆地将配体结合的能量与配体结合的能量偶联，以完成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分，并测量与每个部分相关的能量变化。通过这样做，我们将理解、设计和控制这种受体对药物的反应。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。

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.