Choice of Force Field for Proteins Containing Structured and Intrinsically Disordered Regions.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
07 04 2020
07 04 2020
Historique:
received:
17
04
2019
revised:
06
01
2020
accepted:
05
02
2020
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
15
5
2021
Statut:
ppublish
Résumé
Biomolecular force fields optimized for globular proteins fail to properly reproduce properties of intrinsically disordered proteins. In particular, parameters of the water model need to be modified to improve applicability of the force fields to both ordered and disordered proteins. Here, we compared performance of force fields recommended for intrinsically disordered proteins in molecular dynamics simulations of three proteins differing in the content of ordered and disordered regions (two proteins consisting of a well-structured domain and of a disordered region with and without a transient helical motif and one disordered protein containing a region of increased helical propensity). The obtained molecular dynamics trajectories were used to predict measurable parameters, including radii of gyration of the proteins and chemical shifts, residual dipolar couplings, paramagnetic relaxation enhancement, and NMR relaxation data of their individual residues. The predicted quantities were compared with experimental data obtained within this study or published previously. The results showed that the NMR relaxation parameters, rarely used for benchmarking, are particularly sensitive to the choice of force-field parameters, especially those defining the water model. Interestingly, the TIP3P water model, leading to an artificial structural collapse, also resulted in unrealistic relaxation properties. The TIP4P-D water model, combined with three biomolecular force-field parameters for the protein part, significantly improved reliability of the simulations. Additional analysis revealed only one particular force field capable of retaining the transient helical motif observed in NMR experiments. The benchmarking protocol used in our study, being more sensitive to imperfections than the commonly used tests, is well suited to evaluate the performance of newly developed force fields.
Identifiants
pubmed: 32367806
pii: S0006-3495(20)30168-5
doi: 10.1016/j.bpj.2020.02.019
pmc: PMC7136338
pii:
doi:
Substances chimiques
Intrinsically Disordered Proteins
0
Water
059QF0KO0R
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1621-1633Informations de copyright
Copyright © 2020 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Références
Chembiochem. 2013 Sep 23;14(14):1772-9
pubmed: 23868186
J Chem Phys. 2008 Apr 28;128(16):165106
pubmed: 18447510
Anal Chem. 2013 Feb 5;85(3):1828-33
pubmed: 23297715
J Phys Chem B. 1998 Apr 30;102(18):3586-616
pubmed: 24889800
J Biomol NMR. 2017 Nov;69(3):133-146
pubmed: 29071460
Science. 2017 Oct 13;358(6360):238-241
pubmed: 29026044
J Am Chem Soc. 2009 Dec 16;131(49):17908-18
pubmed: 19908838
Nat Protoc. 2008;3(4):679-90
pubmed: 18388951
Prog Nucl Magn Reson Spectrosc. 2015 Nov;90-91:49-73
pubmed: 26592945
J Biomol NMR. 2010 Nov;48(3):169-77
pubmed: 20890634
J Biol Chem. 2017 Apr 21;292(16):6715-6727
pubmed: 28258221
J Biol Chem. 2018 Aug 24;293(34):13297-13309
pubmed: 29925592
J Biol Chem. 1964 Sep;239:2910-7
pubmed: 14216443
Biophys Chem. 2017 Apr;223:25-29
pubmed: 28282625
Proc Natl Acad Sci U S A. 2018 May 22;115(21):E4758-E4766
pubmed: 29735687
Protein Sci. 2003 Jan;12(1):1-16
pubmed: 12493823
Protein Sci. 2007 Oct;16(10):2108-17
pubmed: 17766372
J Mol Biol. 2004 May 14;338(5):1015-26
pubmed: 15111064
Annu Rev Biochem. 1971;40:465-500
pubmed: 4399447
J Magn Reson. 2014 Apr;241:41-52
pubmed: 24656079
J Biomol NMR. 2013 Aug;56(4):291-301
pubmed: 23877929
J Phys Chem B. 2015 Apr 23;119(16):5113-23
pubmed: 25764013
J Phys Chem Lett. 2016 Jul 7;7(13):2483-9
pubmed: 27300592
J Biomol NMR. 2010 Sep;48(1):13-22
pubmed: 20628786
Biomolecules. 2019 Mar 16;9(3):
pubmed: 30884818
J Proteome Res. 2007 Jun;6(6):2351-66
pubmed: 17488107
Biophys J. 2011 May 4;100(9):L47-9
pubmed: 21539772
J Chem Inf Model. 2017 May 22;57(5):1166-1178
pubmed: 28448138
J Biomol NMR. 2018 Mar;70(3):141-165
pubmed: 29399725
J Am Chem Soc. 2010 Jun 23;132(24):8407-18
pubmed: 20499903
J Chem Phys. 2007 Jan 7;126(1):014101
pubmed: 17212484
Nat Methods. 2017 Jan;14(1):71-73
pubmed: 27819658
Curr Opin Struct Biol. 2011 Jun;21(3):419-25
pubmed: 21514142
J Bacteriol. 2013 Jun;195(11):2603-11
pubmed: 23543716
Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14237-8
pubmed: 18799750
J Appl Crystallogr. 2012 Mar 15;45(Pt 2):342-350
pubmed: 25484842
J Magn Reson. 1998 Apr;131(2):373-8
pubmed: 9571116
Protein Sci. 2002 Apr;11(4):739-56
pubmed: 11910019
Proteins. 2010 Jun;78(8):1950-8
pubmed: 20408171
Biochemistry. 2002 May 28;41(21):6573-82
pubmed: 12022860