Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb:48:40-48.
doi: 10.1016/j.sbi.2017.10.008. Epub 2017 Nov 5.

Force field development and simulations of intrinsically disordered proteins

Jing Huang  1 , Alexander D MacKerell Jr  2
Affiliations
Review

Force field development and simulations of intrinsically disordered proteins

Jing Huang et al. Curr Opin Struct Biol. 2018 Feb.

Abstract

Intrinsically disordered proteins (IDPs) play important roles in many physiological processes such as signal transduction and transcriptional regulation. Computer simulations that are based on empirical force fields have been increasingly used to understand the biophysics of disordered proteins. In this review, we focus on recent improvement of protein force fields, including polarizable force fields, concerning their accuracy in modeling intrinsically disordered proteins. Some recent benchmarks and applications of these force fields are also overviewed.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Variation of dipole moments in (AAQAA)3 during a MD simulation with the Drude polarizable FF. (A) Definition of the peptide bond used to compute backbone dipole moment. (B) Time series of the backbone dipole moment and the sidechain dipole moment of the central Gln residue in (AAQAA)3. (C) The average enhancement of peptide backbone dipole moments in different conformational regions as defined using the backbone ϕ,ψ dihedral angles. Shown are the total dipole moment enhancement, the intra-peptide enhancement (red) and the solvent enhancement (gray). Stronger enhancement of the backbone dipole moment, in particular the intra-peptide enhancement, is observed when a residue folds into an α-helix. Such enhancement provides additional free energy incentive for helix elongation, leading to the reproduction of the experimentally observed folding cooperativity. The enhancement is computed as the difference of the peptide bond dipole moment with and without their environments (water and the remaining part of the peptide). Results are averaged over all peptide bonds in the protein. See Ref. for more details.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Csizmok V, Follis AV, Kriwacki RW, Forman-Kay JD. Dynamic Protein Interaction Networks and New Structural Paradigms in Signaling. Chemical Reviews. 2016;116:6424–6462. - PMC - PubMed
    1. Wright PE, Dyson HJ. Intrinsically disordered proteins in cellular signalling and regulation. Nat Rev Mol Cell Biol. 2015;16:18–29. - PMC - PubMed
    1. Uversky VN, Davé V, Iakoucheva LM, Malaney P, Metallo SJ, Pathak RR, Joerger AC. Pathological Unfoldomics of Uncontrolled Chaos: Intrinsically Disordered Proteins and Human Diseases. Chemical Reviews. 2014;114:6844–6879. - PMC - PubMed
    1. Brucale M, Schuler B, Samorì B. Single-Molecule Studies of Intrinsically Disordered Proteins. Chemical Reviews. 2014;114:3281–3317. - PubMed
    1. Jensen MR, Zweckstetter M, Huang, Blackledge M. Exploring Free-Energy Landscapes of Intrinsically Disordered Proteins at Atomic Resolution Using NMR Spectroscopy. Chemical Reviews. 2014;114:6632–6660. - PubMed

Publication types

LinkOut - more resources