Bridging the Gap Between Optical Spectroscopic Experiments and Computer Simulations for Fast Protein Folding Dynamics

Raymond      Z. Cui; Daniel-Adriano      Silva; Jian      Song; Gregory      R. Bowman; Wei      Zhuang; Xuhui      Huang

Abstract

Fast folding techniques use optical spectroscopic tools to monitor protein folding or unfolding dynamics after a fast triggering such as the laser induced temperature jump. These techniques have greatly improved time resolution of experiments and provide new opportunities for comparison between theory and simulations. However, the direct comparison is still difficult due to two main challenges: a gap between folding relevant timescales (microseconds or above) and length of molecular dynamics simulations (typically tens to hundreds of nanoseconds), and difficulty in directly calculating spectroscopic observables from simulation configurations. This review is focused on recent advances in addressing these two challenges. We describe new methodology that allows simulating folding timescales with an emphasis on Markov State Models. We also review progress on modeling infrared, circular dichroism, and fluorescence spectroscopic signals from protein conformations. At last, we discuss a few studies that directly simulate time-resolved spectroscopy of temperature jump induced unfolding dynamics for a few small proteins. These studies not only provide direct validation of theoretical models, but also greatly improve our understanding of protein folding mechanisms by connecting ensemble averaged spectroscopic observables with atomistic protein conformations.

Keywords: Protein folding, Optical spectroscopy, Molecular dynamics simulations, Markov state model, photochemical reaction, FLUORESCENCE SPECTROSCOPY, DICHROISM, rotational strength, INFRARED (IR) SPECTROSCOPY, electronic excitations