Comparison and Evaluation of Force Fields for Intrinsically Disordered Proteins
Mueed Ur Rahman1, Ashfaq Ur Rehman1, Hao Liu1
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Journal of Chemical Information and Modeling
|August 21, 2020
Summary
Molecular dynamics simulations reveal that intrinsically disordered protein (IDP)-specific force fields better reproduce experimental data for IDPs compared to general force fields. These IDP-specific force fields show promise for future protein simulations.
Area of Science:
- Computational Chemistry
- Biophysics
- Structural Biology
Background:
- Molecular dynamics (MD) simulations are crucial for understanding protein dynamics.
- Empirical force fields significantly influence simulation accuracy.
- Previous studies highlight variability in MD outcomes due to different force fields, water models, and parameters.
Purpose of the Study:
- To evaluate and compare six upgraded empirical force fields for molecular dynamics (MD) simulations.
- To assess the performance of these force fields using various systems including short peptides, intrinsically disordered proteins (IDPs), and folded proteins.
- To compare simulation-generated ensembles against experimental Nuclear Magnetic Resonance (NMR) data.
Main Methods:
- MD simulations were conducted in explicit solvent for systems like RS-peptide, HEWL19, HIV-rev, β amyloid (Aβ)-40, Aβ-42, phosphodiesterase-γ, CspTm, and ubiquitin.
- Six all-atom empirical force fields were tested: ff99IDPs, ff14IDPs, ff14IDPSFF, ff03w, CHARMM36m, and CHARMM22*.
- Simulations utilized trajectories of 1 to 10 μs, with multiple replicates for each system.
Main Results:
- Different force fields produced significantly different ensembles, impacting NMR RMDs, secondary structure content, and radius of gyration.
- IDP-specific force fields demonstrated superior performance, yielding the lowest error in chemical shifts and J-couplings for peptides/proteins.
- IDP-specific force fields accurately captured the disordered nature of IDPs and showed a fraction of beta sheets for beta-amyloids, performing comparably to CHARMM22* for folded proteins.
Conclusions:
- IDP-specific force fields are essential for accurately simulating intrinsically disordered proteins.
- The evaluated force fields show comparable performance for folded proteins.
- These findings contribute to the ongoing development and refinement of force fields for both disordered and folded proteins in MD simulations.
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