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.
