CAREER: Electrostatic Mechanisms in Protein Stability and Folding

本CAREER项目的目标是开发和应用新的理论方法和分子模拟技术来表征变性状态，并辨别残基特定静电对模型蛋白稳定性的贡献，包括NTL9， HP36和亮氨酸拉链。本研究将解决阻碍变性和无序蛋白质理论研究的两个突出问题，即缺乏严格的手段来验证微观信息和力场偏差问题。静电相互作用在生物功能中起着重要作用。然而，目前对静电效应的认识是不完整的。这是因为实验技术不能隔离静电贡献，而现有理论研究的准确性不足。开发的模拟工具和软件将向社区传播，以推进静电现象和许多涉及变性状态和无序蛋白质的重要生物过程的原子水平研究。为了帮助培养具有先进科学知识、批判性思维和解决问题能力的新一代劳动力，PI将开发新的课程，将课堂教学和实践研究项目结合起来。更广泛的教育影响还包括一个网站（http://computchem.org），专门为那些有兴趣学习和应用理论和计算工具来解决生物、化学和物理等跨学科领域的问题的学生。现代交流工具如博客、论坛、维基和媒体被提供，以促进世界范围内社区的同侪学习和知识共享。PI将举办研讨会和接待暑期实习生，以进一步提高学习经验，并增加代表性不足的少数民族学生的参与。

The objective of this CAREER project is to develop and apply new theoretical methods and molecular simulation techniques to characterize the denatured states and to discern residue-specific electrostatic contributions to the stability of model proteins including NTL9, HP36 and leucine zippers. This research will tackle two outstanding problems that hamper theoretical studies of denatured and disordered proteins, namely, the lack of rigorous means to validate microscopic information and the problem of force field bias. Electrostatic interactions play an important role in biological functions. However, the current knowledge of electrostatic effects is incomplete. This is because experimental techniques cannot isolate electrostatic contributions, while the accuracy of existing theoretical studies is insufficient. The developed simulation tools and software will be disseminated to the community to advance atomic-level studies of electrostatic phenomena and many important biological processes involving denatured states and disordered proteins.To help prepare a new generation of work force with state-of-the-art scientific knowledge as well as critical thinking and problem solving skills, the PI will develop new curricula that integrate classroom teaching and hands-on research projects. The broader educational impacts also include a web site (http://computchem.org) dedicated to students who are interested in learning and applying theoretical and computational tools to problems in the cross-disciplinary areas of biology, chemistry, and physics. Modern communication tools such as Blogs, Forums, Wikis, and Media are offered to promote peer learning and knowledge sharing in a world-wide community. The PI will give seminars and host summer interns to further enhance learning experience and to increase participation of underrepresented minority students.