Petascale Simulations of Biomolecular Function and Conformational Change

大约有7000万美国人患有慢性疼痛-超过糖尿病，心脏病和癌症的总和。然而，疼痛的根本原因仍然不清楚，除了服用阿片类药物和密切相关的药物外，患者几乎没有其他治疗选择。然而，类阿片往往导致产生耐受性和依赖性，因此其治疗功效受到严重限制。随着近700万美国人滥用处方止痛药），从基础研究领域向临床应用的推动现在比以往任何时候都更加紧迫。开发安全的阿片类镇痛剂是这一宏伟目标的首要任务。1）揭示μ-阿片受体（μ-OR）疼痛信号机制的细节-身体疼痛管理的关键蛋白质-并推动非成瘾性阿片类镇痛药的开发，（2）开发一种技术，使科学界的其他研究小组能够研究类似的大型和复杂的生物系统。

Roughly 70 million Americans suffer from chronic pain - more than from diabetes, heart disease and cancer combined. Yet the fundamental causes of pain are still not understood and patients are left with few treatment options other than the administration of opiates and closely related drugs. Opioids, however, often lead to the development of tolerance and dependence, and are thus severely limited in their treatment efficacy. With nearly 7 million Americans abusing prescription painkillers), a push from the sphere of basic research toward clinical applications is now more pressing than ever. The development of safe opioid analgesics is at the forefront of this ambition.This project's objective is two-fold: 1) uncover details in the pain signaling mechanism of the µ-opioid receptor (µ-OR) - a key protein in the management of pain in the body - and push the development of non-addictive opioid analgesics, and 2) develop a technology that will enable the study of similarly large and complex biological systems by other research groups in the scientific community.