Folding dynamics of a small protein at room temperature via simulated coherent two-dimensional infrared spectroscopy

Abstract

Understanding protein folding is of fundamental and practical importance in chemistry and biology. Despite the great success that has been made in tackling this problem, a detailed knowledge of how the elementary processes such as hydrogen-bond formation occur during protein folding has remained largely elusive. Using the combined power of molecular dynamics simulation with electrostatic polarization and coherent two-dimensional infrared spectroscopy, we are able to delineate the order of the hydrogen-bond formation event of a 17-residue peptide during its folding from an extended state to the native α-helix state. The folding is carried out by a single trajectory room-temperature molecular dynamics simulation that includes the polarization effect of hydrogen bonding, which is critical to the successful folding of the peptide. The onset and evolution of the isotope-labeled amide I vibration diagonal and cross peaks on the simulated 2DIR spectra allow us to build a structure-spectrum connection, and thus provide a microscopic picture of the helix folding process.

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

“…59 This is due to the formation of the secondary structure and hydrogen bonds, as shown in Table 1, which weakens the CO bond and reduces its vibrational frequency. 5 The peak intensity decreases from L1 to L50 and then increases from L50 to L100, which indicates that ordered structures, including the linear extended structure and folded structures, tend to enhance the intensity. Since the contributions from the isotope-labeled residues are much weaker than those from the unlabeled residues, we enlarge the spectral region corresponding to isotope-labeled amide I modes in Figure 4b−f.…”

Molecular Dynamics Simulation and Computational Two-Dimensional Infrared Spectroscopic Study of Model Amyloid β-Peptide Oligomers

“…In the past decade, coherent two-dimensional infrared spectroscopy (2DIR) − has emerged as a promising technique that enables us to probe changes in the secondary structure of proteins at unprecedented time resolution, picosecond or even femtosecond. This was made possible by using ultrafast laser pulses.…”

Treatment of Hydrogen Bonds in Protein Simulations

“…[34] PPC is derived from first principle quantum calculation and therefore can correctly represent the electronically polarized state of the protein. It has been proven that the polarization effect plays an important role in pK a shifts for ionizable residues, [34] hydrogen bond stability, [35,40] protein folding, and native structure stabilization, [17,41,45] dynamic properties of proteins, [46,48] protein-ligand binding affinity, [47,49,51] and protein-protein recognition specificity. [52] The polarization of backbone hydrogen bonding is found critical to the success of folding simulation of proteins.…”