Accelerated Molecular Dynamics for Peptide Folding: Benchmarking Different Combinations of Force Fields and Explicit Solvent Models

Abstract

Accelerated molecular dynamics (aMD) protocols were assessed on predicting the secondary structure of eight peptides, of which two are helical, three are β-hairpins, and three are disordered. Protocols consisted of combinations of three force fields (ff99SB, ff14SB, ff19SB) and two explicit solvation models (TIP3P and OPC), and were evaluated in two independent aMD simulations, one starting from an extended conformation, the other starting from a misfolded conformation. The results of these analyses indicate that all three combinations performed well on helical peptides. As for β-hairpins, ff19SB performed well with both solvation methods, with a slight preference for the TIP3P solvation model, even though performance was dependent on both peptide sequence and initial conformation. The ff19SB/OPC combination had the best performance on intrinsically disordered peptides. In general, ff14SB/TIP3P suffered the strongest helical bias.

Energy Landscapes and Structural Ensembles of Glucagon-like Peptide-1 Monomers

“…Care must be taken not to overinterpret the results from computational simulation. The force field and solvent model selected are standard for current peptide-based modeling, and, despite this combination being the recommendation of AMBER developers, a helical bias has been noted. , To validate the choice of solvation model, the stability of distinct minima was tested with explicit solvent molecular dynamics simulations, which demonstated stability of the predicted structures (see Supporting Information, Figures S7 to S12). Restricting simulations to monomers only was a further limitation, as GLP‑1 in solution coexists in an equilibrium of monomeric and oligomeric forms .…”

Can Duvelisib and Eganelisib work for both cancer and COVID-19? Molecular-level insights from MD simulations and enhanced samplings

“…During the production run, the coordinates were saved every 10 ps. As the TIP3P water model is more compatible with the AMBER force field, 36,39,40 some systems were simulated for 500 ns again in such water. In contrast to SPC, the TIP3P water model possesses a larger dipole moment and has a bond angle and dielectric constant closer to the experimental values.…”