Protein folding is an important biological process because proteins are required to fold into unique structures for proper functionality in cells. Experiments on living specimens are difficult to perform because of the interference from complex interactions in a cell. The aim of this project is to investigate statistical and kinetic properties of protein folding in the presence of crowding agents using a combined experimental and computational approach. Studies of such complex systems covering several orders of magnitude in spatial and temporal scales require techniques from coarse-grained molecular simulation and fine-grained atomistic simulations. These methods will be strategically integrated into a multi-scale approach which enables the investigation of protein dynamics in realistic conditions. The knowledge obtained from the research will be used to discover physical principles of protein folding in vivo and predict new phenomena that can only be seen in the interior of a cell. An integrated multi-scale modeling and simulation approach will be applied to enhance knowledge of complex protein dynamics in living systems. The project will advance international research collaboration with the experimental group of Dr. Pernilla Wittung-Stafshede in Sweden.
This project will involve training of undergraduate and graduate students through hands-on research in the interdisciplinary fields of physics, chemistry and biology at the University of Houston, one of the most ethnically diverse research universities in the country. Students will learn about paradigms for high-performance computing, algorithms for molecular simulations, and physical principles to better understand biological systems at a molecular level. Newly developed multiscale modeling and simulation software will be made available to the scientific community through the internet. The PI plans to include the use of this software in her regular visits to high schools in the Houston area and to continue encouragement of women and underrepresented groups to pursue careers in sciences and engineering. The PI also plans to host summer educational workshops for undergraduate students and high school teachers that will provide participants with hands-on experience in applying this software to biophysics research as an effective teaching and learning approach to impact science education.
". One postdoctoral associate, three graduate students, and three undergraduate students were trained during this period. A total of 11 papers and 2 proceedings have resulted from the content of the research. Intellectual Merit: Proteins are workhorses in a cell. How it folds from a string-like conformation into a compact and biologically functional structure in a crowded environment is not well understood. We used and developed computational methods and physical theories to study protein folding in a cell-like environment. We collaborated with the experimental groups who validated the theoretical and computational predictions from our studies in two fronts: (1) the macromolecular crowding effect induces shape changes in and impacts the function of proteins; (2) the macromolecular crowding effect enhances the native state and likely alters the folding routes. Broader Impact: (Outreach) I have started a professional development program for high-school teachers, Physics Science Teaching Equity Project (Physics STEP). In collaboration with the College of Education (http://step.coe.uh.edu/Physics.html), we developed an inquiry-based approach for learning several key physics concepts at an appropriate grade level through economical hands-on experiments. Each year this program recruits 20 in-service non-physics teachers from high-need school districts that recognized their effort as part of the professional development. The teachers from the Physics STEP program implemented these inquiry-based approaches in their class preparation and taught over 3000 high school students. In the summer, we recruited a group of physics faculty members and their graduate students. They hosted these teachers in their research groups and showed them the applications of physics research in the real world. In addition, through the network of K-12 science teachers, I have hosted science field trips for the students to visit the UH campus and attended the Career Days at their schools, reaching out to over 500 young students. (Mentoring) I have actively recruited and mentored the research of nine undergraduate students. Five of these undergraduate students (including four women) were from the underrepresented groups. Two of these students are also co-authors on my papers. (Software) I have integrated the coarse-grained molecular simulation into a distributed computational platform that allows parallel execution of the computation of protein folding under cell-like conditions. The inCell@home is a volunteer-based computational system that is available to the general public and high school students for science computing and data analysis.
