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

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.

Folding@home: Achievements from over 20 years of citizen science herald the exascale era

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Low frequency 2D Raman-THz spectroscopy of ionic solution: A simulation study

“…[22][23][24][25][26][27][28][29] Experimental and theoretical work on 2D infrared spectrum has been employed to study a series of important dynamical behavior in aqueous solution with ions and biomolecules lately. [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] Recently, a novel 2D spectroscopy, 2D Raman-THz spectroscopy, [45][46][47] has been proposed to probe the collective dynamics in the pure water as well as the aqueous solutions. Such technique reveals similar information as 2D Raman and 2D THz spectroscopies and is, in particular, powerful in studying the coupling of the vibrational modes that are both infrared (IR) and Raman active.…”