Accurate atomistic simulation of large conformational changes of proteins remains one of the greatest challenges in computational biology. Implicit treatment of the solvent environment has recently emerged as the premier alternative to traditional explicit solvent with a desired balance between accuracy and speed. The objective of this CAREER project is to develop, optimize and assess novel implicit treatments of nonpolar solvation to better balance competing electrostatic and nonpolar interactions. The second objective is to combine simulation and experiment to understand the structure, interaction and control of intrinsically disordered proteins (IDPs). IDPs are an important newly recognized class of functional proteins that rely on a lack of stable structures for function. The heterogeneous and dynamic nature of IDPs presents significant challenges for detailed characterization with either experiment or simulation alone. The PI will combine implicit solvent modeling, advanced sampling techniques, and NMR experiment to address these challenges. A novel hypothesis to be tested is that long- range electrostatic interactions can act concertedly with fly-casting to facilitate efficient recognition of IDPs. New and fundamental information will be obtained on the molecular principles of IDP structure and interaction. A practical outcome of this project will be an improved implicit solvent protein force field that can be broadly applied to study protein structure, dynamics and interaction.
The new protein modeling tools will be directly incorporated into training and educational activities including practical course units, training projects involving undergraduate and high school students, and summer workshops for a diverse selection of participants. Specifically, the PI will: 1) develop and revamp undergraduate and graduate courses to increase interdisciplinary awareness at an early stage of education and to provide basic training in biomolecular simulation that is much needed at Kansas State University (KSU); 2) continue to actively contribute to outreach programs at KSU including Women in Engineering and Science Program, Developing Scholar Program and Bridges to the Baccalaureate to increase the participation of women and other minorities in science; 3) initiate annual two-day summer workshops to enhance the knowledge of computational and structural biology for college and high school teachers. Special emphasis will be placed on recruiting teachers from community colleges in southern Kansas that have a large Hispanic student population and traditionally show weakness in student preparation. These workshops will help foster new collaborations in research and education with minority-severing institutions.
