Effects of macromolecular crowding on protein structure, folding, and interactions

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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.