Evaluation of the Coupled Two-Dimensional Main Chain Torsional Potential in Modeling Intrinsically Disordered Proteins

Abstract

Intrinsically disordered proteins (IDPs) carry out crucial biological functions in essential biological processes of life. Because of the highly dynamic and conformationally heterogeneous nature of the disordered states of IDPs, molecular dynamics simulations are becoming an indispensable tool for the investigation of the conformational ensembles and dynamic properties of IDPs. Nevertheless, there is still no consensus on the most reliable force field in molecular dynamics simulations for IDPs hitherto. In this work, the recently proposed AMBER99SB force field is evaluated in modeling some disordered polypeptides and proteins by checking its ability to reproduce experimental NMR data. The results highlight that when the ildn side-chain corrections are included, AMBER99SB-ildn exhibits reliable results that agree with experiments compared with its predecessors, the AMBER14SB, AMBER99SB, AMBER99SB-ildn, and AMBER99SB force fields, and that decreasing the overall magnitude of protein-protein interactions in favor of protein-water interactions is a key ingredient behind the improvement.

The IDP-Specific Force Field ff14IDPSFF Improves the Conformer Sampling of Intrinsically Disordered Proteins

“…Among these IDPs, IA3 is also investigated by Mei and co-workers with AMBER99SB 2D force field and the helical structure rapidly unfolds, whose simulations are extended to 1000 ns. 54 For unstructured short peptides, the RMSD’s between predicted and measured chemical shifts for ff14IDPSFF are also significantly less than those for ff14SB . Of course there are still some differences between simulation and experiment, with the largest deviations mainly in KID and HIVRev.…”

“…This confirms our systematic strategy to correct the biases embedded in generic protein force fields by targeting the coil regions of known protein structures. Among these IDPs, IA3 was also investigated by Mei and co-workers with the AMBER99SB 2D force field, and the helical structure rapidly unfolds, whose simulations are extended to 1000 ns . For unstructured short peptides, the RMSDs between predicted and measured chemical shifts for ff14IDPSFF are also significantly less than those for ff14SB .…”

AMBER and CHARMM Force Fields Inconsistently Portray the Microscopic Details of Phosphorylation

“…Molecular dynamics simulations with atomistic force fields offer a straightforward approach to generate a structural ensemble under experimental constraints. However, the ability of current force fields to reproduce the properties of IDPs is limited and depends heavily on parametrization. − Additionally, amino acids with PTMs are rarely represented in computational studies of proteins. In the past, parameters for PTM residues were often developed independently of the parental force fields, mostly relying on the transferability of parameters from model compounds.…”

Atomistic simulation of the coupled adsorption and unfolding of protein GB1 on the polystyrenes nanoparticle surface

“…It has been shown to perform well by many works [48][49][50][51] . However, it was also reported to tend to increase helical content 52 , encourage global contacts 53 , give stronger interaction of ARG and LYS with the lipid phosphate groups, or generally overestimate the potential energy of protein-protein interactions at the expense of water-water and water-protein interactions [54][55] . The results presented here may be affected by these potential flaws.…”