Colin A. Smith, Asst Professor, Dept of Chemistry; Dept of Molecular Biology & Biochemistry; and School of Integrative Sciences, Wesleyan University, will give a talk titled:   ​​​​​​​"Elucidating Effects of Motion on Designed Fluorescent Proteins through Simulation and Improved Modeling of NMR Data"

ABSTRACT

The de novo computational design of proteins with a predefined three-dimensional structure is becoming routine. However, giving those molecules useful functions is often much more difficult. In that regard, the recent design of proteins that activate the fluorescence of a small molecule chromophore is noteworthy. The design process created a large library of variants, but gave no rational explanation of why one variant is brighter than another. Using both quantum mechanics and molecular dynamics simulations, we show that the ability of the protein to resist chromophore motion can predict brightness. In addition to providing avenues for optimizing these proteins, this represents an ideal model system for studying how to design proteins that stabilize a particular ligand conformation, a critical aspect of enzyme design. To further characterize the solution dynamics of this and other proteins in full-atom detail, we are developing new computational techniques that can extract dynamics from nuclear Overhauser effect (NOE) experiments used for structure determination. Due to numerous approximations, those structures often have limited accuracy and many aspects of inherent protein flexibility are neglected. To overcome this, we recently developed a new computational method, called the Kinetic Ensemble approach, that rigorously quantifies protein motion from NOE data.