Monitoring the Folding of Trp-Cage Peptide by Two-Dimensional Infrared (2DIR) Spectroscopy

Abstract

Protein folding is one of the most fundamental problems in modern molecular biology. Uncovering the detailed folding mechanism requires methods that can monitor the structures at high temporal and spatial resolution. Two-dimensional infrared (2DIR) spectroscopy is a new tool for studying protein structures and dynamics with high time resolution. Using atomistic molecular dynamics simulations, we illustrate the folding process of Trp-cage along the dominant pathway on free energy landscape by analyzing nonchiral and chiral coherent 2DIR spectra along the pathway. Isotope-labeling is used to reveal residue-specific information. We show that the high resolution structural sensitivity of 2DIR can differentiate the ensemble evolution of protein, and thus provides a microscopic picture of the folding process.

Two-dimensional infrared spectroscopy of vibrational polaritons of molecules in an optical cavity

“…Coherent multidimensional infrared spectroscopy is a powerful time domain tool that can probe anharmonicities and vibrational energy relaxation pathways [20][21][22][23][24] . Vibrational polaritons were experimentally reported 6,8,9 and calculated 7,25 recently.…”

Two-dimensional stimulated resonance Raman spectroscopy study of the Trp-cage peptide folding

“…Trp-cage is a mini-protein contains 20 residues with the sequence “NLYIQWLKDGGPSSGRPPPS”. Its fast nanosecond folding makes it a convenient model system for experimental and computational investigations [21, 58–60]. Spectra with various pulse polarization configurations were simulated at different folding stages obtained by molecular dynamics (MD) simulations and trajectory analysis.…”

Achieving Rigorous Accelerated Conformational Sampling in Explicit Solvent

“…The freeenergy plots were projected onto various local and global collective variables that provide information about the folding of the different regions of the protein as well as the overall protein. Despite several experimental 53 24,25,35,62,63,65,66,68,69 there is still no agreement on the nature of this intermediate.…”