Tetrapeptide unfolding dynamics followed by core-level spectroscopy: a first-principles approach

Area of Science:

• Computational Chemistry
• Spectroscopy
• Biophysics

Background:

• Understanding polypeptide dynamics and conformational changes is crucial in molecular biology and drug discovery.
• Established spectroscopic techniques can be limited in their ability to fully resolve complex molecular dynamics.

Purpose of the Study:

• To demonstrate the utility of core level analysis, specifically sulphur 1s core level shifts (S1s CLS), for distinguishing polypeptide conformations.
• To investigate the S1s CLS of a model tetrapeptide (cysteine-phenylalanine-tyrosine-cysteine) in various folding states using computational simulations.

Main Methods:

• Employed computer simulations utilizing initial and final state approximations for S1s CLS calculations.
• Applied a range of electronic structure methods, including Hartree-Fock, density functional theory, and configuration interaction.
• Utilized a multiscale algorithm to enhance computational efficiency for electronic structure calculations.

Main Results:

• Distinct peptide arrangements exhibited significantly different S1s CLS (over 0.5 eV) compared to the reference disulfide bridge state.
• The study successfully correlated specific S1s CLS values with different folding configurations of the CYFC tetrapeptide.

Conclusions:

• Core level analysis provides a powerful and sensitive method for disentangling polypeptide dynamics and conformational changes.
• The proposed computational approach yields experimentally detectable signals and offers a potential alternative to existing spectroscopic techniques.