(194b) Simple and Accurate Method to Calculate Circular Dichroism Spectra of Peptides and Proteins in Molecular Dynamics Simulations

Circular dichroism spectroscopy is an efficient and widely used tool to probe the secondary structure of chiral organic molecules and biomacromolecules such as peptides and proteins. Comparisons between molecular models from simulations and experimental measurements are essential to advance understanding of complex biological molecules, assemblies, and multiphase biomaterials. In this work, a simple and accurate method to calculate CD spectra from the timeline of molecular dynamics trajectories is introduced and validated. The secondary structure of the concerned peptide or protein is analyzed during the molecular dynamics trajectory in equilibrium and percentages of time are specified for each secondary structure motif, including alpha-helix, 3,10-helix, beta-sheet, coil, turn, and polyproline helix (PPII). Then, experimental standard ellipticity data for each secondary structure are used to compute the CD spectrum as a linear combination of reference CD spectra with the percentages of time as a weight factor. Compared to earlier methods, this method includes the polyproline helix (PPII), which has a significant impact on the computed CD spectra. The analysis of secondary structures can be performed using VMD timeline in the VMD program for all structural elements excluding PPII, and the PPII content can be determined manually. The method was tested by the calculation of CD spectra for several single peptides and proteins in solution with experimental reference CD spectra, as well as for peptides adsorbed on surfaces (MoS₂, silica, hydroxyapatite) using the Interface Force Field (CHARMM-IFF) with experimental reference CD spectra. The results show excellent agreement in all cases. The method can be applied as a simple and powerful tool in computer-aided structural biology and biomaterial design.