GaMD simulations as an alternative in the TFE-water mixture description

Area of Science:

• Computational Chemistry
• Biophysics
• Protein Dynamics

Background:

• 2,2,2-Trifluoroethanol (TFE) mixtures are crucial for studying intrinsically disordered proteins (IDPs).
• TFE-water mixtures stabilize secondary structures, enabling conformational ensemble analysis.
• Conventional molecular dynamics (MD) simulations face challenges in accurately modeling TFE-water mixtures, particularly TFE nanocrowding.

Purpose of the Study:

• To identify optimal simulation conditions for accurately reproducing experimental properties of TFE-water mixtures.
• To compare conventional MD and Gaussian accelerated molecular dynamics (GaMD) simulations using various water models.

Main Methods:

• Conventional MD and GaMD simulations were performed using AMBER 18.
• GAFF2 force field described TFE; TIP3P, TIP4P2005, TIP4PD, and TIP5P models described water.
• Simulations were conducted at 298 K for 100 ns.

Main Results:

• The combination of the TIP4PD water model and GaMD simulations best reproduced experimental data for TFE-water mixtures.
• This specific parameter set effectively captures the TFE-water mixture properties.

Conclusions:

• The TIP4PD water model with GaMD simulations provides an accurate method for studying IDPs in TFE-water mixtures.
• This approach enhances the description of IDP structural ensembles in these solutions.