Force Field Effects in Simulations of Flexible Peptides with Varying Polyproline II Propensity

Five peptides previously suggested to possess polyproline II (PPII) structure have here been investigated by using atomistic molecular dynamics simulations to compare how well four different force fields known for simulating intrinsically disordered proteins relatively well (Amber ff99SB-disp, Amber ff99SB-ILDN, CHARM36IDPSFF, and CHARMM36m) can capture this secondary structure element. The results revealed that all force fields sample PPII structures but to different extents and with different propensities toward other secondary structure elements, in particular, the beta-sheet and random coils. A cluster analysis of the simulations of histatin 5 also revealed that the conformational ensembles of the force fields are quite different. We compared the simulations to circular dichroism and nuclear magnetic resonance spectroscopy experiments and conclude that further experiments and methods for interpreting them are needed to assess the accuracy of force fields in determining PPII structure.

Automated summary

This study compared the performance of four different force fields in simulating the PPII structure of five peptides, revealing that all force fields are able to capture PPII structures but with varying degrees of affinity to other secondary structure elements. Cluster analysis of simulations showed significant differences in the conformational ensembles of the force fields, indicating a need for further experiments and methods to assess the accuracy of force fields in determining PPII structure.