CAREER: Electrostatic Mechanisms in Protein Stability and Folding

这个职业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，并识别特定残基的静电对模型蛋白质稳定性的贡献，包括NTL9、HP36和亮氨酸拉链。这项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，即缺乏验证微观信息的严格手段和力场偏差问题。静电相互作用在生物功能中起着重要的作用。然而，目前关于静电效应的知识是不完整的。这是因为实验技术不能分离出静电贡献，而现有的理论研究的准确性不够。开发的模拟工具和软件将被分发给社会，以促进对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的研究。为了帮助新一代劳动人口培养具有最先进的科学知识以及批判性思维和解决问题的技能，国际和平研究所将开发结合课堂教学和实践研究项目的新课程。更广泛的教育影响还包括一个网站(http://computchem.org))，专门面向那些对学习和应用理论和计算工具解决生物、化学和物理跨学科领域的问题感兴趣的学生。提供了博客、论坛、维基和媒体等现代交流工具，以促进全球社区的同行学习和知识共享。国际学生联合会将举办研讨会和招待暑期实习生，以进一步增强学习经验，并增加未被充分代表的少数族裔学生的参与。

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.