Machine learning coarse-grained potentials of protein thermodynamics.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 09 2023
15 09 2023
Historique:
received:
02
06
2023
accepted:
29
08
2023
medline:
18
9
2023
pubmed:
16
9
2023
entrez:
15
9
2023
Statut:
epublish
Résumé
A generalized understanding of protein dynamics is an unsolved scientific problem, the solution of which is critical to the interpretation of the structure-function relationships that govern essential biological processes. Here, we approach this problem by constructing coarse-grained molecular potentials based on artificial neural networks and grounded in statistical mechanics. For training, we build a unique dataset of unbiased all-atom molecular dynamics simulations of approximately 9 ms for twelve different proteins with multiple secondary structure arrangements. The coarse-grained models are capable of accelerating the dynamics by more than three orders of magnitude while preserving the thermodynamics of the systems. Coarse-grained simulations identify relevant structural states in the ensemble with comparable energetics to the all-atom systems. Furthermore, we show that a single coarse-grained potential can integrate all twelve proteins and can capture experimental structural features of mutated proteins. These results indicate that machine learning coarse-grained potentials could provide a feasible approach to simulate and understand protein dynamics.
Identifiants
pubmed: 37714883
doi: 10.1038/s41467-023-41343-1
pii: 10.1038/s41467-023-41343-1
pmc: PMC10504246
doi:
Substances chimiques
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5739Informations de copyright
© 2023. Springer Nature Limited.
Références
J Chem Phys. 2020 May 21;152(19):194106
pubmed: 33687259
J Phys Chem B. 2005 Feb 24;109(7):2469-73
pubmed: 16851243
Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10141-6
pubmed: 16006532
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Nature. 2005 Nov 3;438(7064):117-21
pubmed: 16267559
J Chem Theory Comput. 2009 Jun 9;5(6):1632-9
pubmed: 26609855
J Chem Theory Comput. 2019 Apr 9;15(4):2719-2733
pubmed: 30810317
J Chem Phys. 2013 Sep 7;139(9):090901
pubmed: 24028092
J Chem Theory Comput. 2016 Apr 12;12(4):1845-52
pubmed: 26949976
J Chem Theory Comput. 2013 Apr 9;9(4):2000-2009
pubmed: 23750122
J Chem Phys. 2018 Jul 21;149(3):034101
pubmed: 30037247
J Chem Theory Comput. 2020 Jul 14;16(7):4685-4693
pubmed: 32539384
J Chem Theory Comput. 2008 May;4(5):819-34
pubmed: 26621095
Nat Commun. 2021 Nov 25;12(1):6884
pubmed: 34824254
Phys Rev Lett. 2012 Feb 3;108(5):058301
pubmed: 22400967
J Comput Chem. 1999 Jun;20(8):786-798
pubmed: 35619462
Chem Sci. 2017 Apr 1;8(4):3192-3203
pubmed: 28507695
Annu Rev Biophys. 2013;42:73-93
pubmed: 23451897
Nat Chem. 2017 Oct;9(10):1005-1011
pubmed: 28937668
Nat Struct Biol. 2000 Aug;7(8):669-73
pubmed: 10932252
Curr Opin Struct Biol. 2004 Feb;14(1):76-88
pubmed: 15102453
J Chem Phys. 2022 Sep 14;157(10):104102
pubmed: 36109216
ACS Cent Sci. 2019 May 22;5(5):755-767
pubmed: 31139712
J Chem Phys. 2015 Dec 28;143(24):243104
pubmed: 26723589
Nature. 2007 Dec 13;450(7172):964-72
pubmed: 18075575
J Chem Phys. 2011 May 7;134(17):174105
pubmed: 21548671
J Chem Phys. 2004 Jul 1;121(1):415-25
pubmed: 15260562
J Chem Theory Comput. 2021 Apr 13;17(4):2355-2363
pubmed: 33729795
Science. 2021 Aug 20;373(6557):871-876
pubmed: 34282049
J Chem Theory Comput. 2019 Jan 8;15(1):448-455
pubmed: 30481453
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):5915-20
pubmed: 23503848
J Chem Inf Model. 2010 Mar 22;50(3):397-403
pubmed: 20199097
J Chem Theory Comput. 2019 Jun 11;15(6):3678-3693
pubmed: 31042390
Nature. 1975 Feb 27;253(5494):694-8
pubmed: 1167625
Proc Natl Acad Sci U S A. 2020 Sep 29;117(39):24061-24068
pubmed: 32929015
Biophys J. 2008 Feb 1;94(3):726-36
pubmed: 17890394
J Phys Chem B. 2013 Oct 24;117(42):12935-42
pubmed: 23882999
J Mol Biol. 2000 May 19;298(5):937-53
pubmed: 10801360
Nature. 1977 Jun 16;267(5612):585-90
pubmed: 301613
J Chem Phys. 2008 Aug 14;129(6):064107
pubmed: 18715051
Curr Opin Struct Biol. 2001 Apr;11(2):224-30
pubmed: 11297932
J Chem Phys. 2008 Oct 14;129(14):144108
pubmed: 19045135
Nucleic Acids Res. 2003 Jul 1;31(13):3370-4
pubmed: 12824330
J Am Chem Soc. 2018 Feb 21;140(7):2386-2396
pubmed: 29323881
Annu Rev Biochem. 2008;77:363-82
pubmed: 18410248
Science. 2019 Sep 6;365(6457):
pubmed: 31488660
J Chem Phys. 2021 Aug 28;155(8):084101
pubmed: 34470360
Nat Struct Mol Biol. 2004 Feb;11(2):135-41
pubmed: 14730350
J Chem Theory Comput. 2022 Oct 11;18(10):5759-5791
pubmed: 36070494
Phys Rev Lett. 2007 Apr 6;98(14):146401
pubmed: 17501293
Nat Commun. 2023 Sep 15;14(1):5739
pubmed: 37714883
Science. 2011 Oct 28;334(6055):517-20
pubmed: 22034434
Science. 1991 Dec 13;254(5038):1598-603
pubmed: 1749933
Nat Struct Biol. 2002 Sep;9(9):646-52
pubmed: 12198485
J Chem Phys. 2020 Sep 28;153(12):124111
pubmed: 33003742
Curr Opin Struct Biol. 2008 Apr;18(2):154-62
pubmed: 18378442
J Chem Phys. 2020 Oct 28;153(16):164501
pubmed: 33138411
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12562-6
pubmed: 12271136
J Chem Phys. 2018 Jun 28;148(24):241722
pubmed: 29960322
Curr Opin Struct Biol. 2004 Feb;14(1):89-95
pubmed: 15102454
Curr Opin Struct Biol. 2023 Apr;79:102533
pubmed: 36731338
PLoS Comput Biol. 2010 Jun 24;6(6):e1000827
pubmed: 20585614
J Chem Theory Comput. 2014 May 13;10(5):2064-9
pubmed: 26580533
J Am Chem Soc. 2004 Jul 14;126(27):8426-32
pubmed: 15237999
J Chem Theory Comput. 2018 Jan 9;14(1):453-460
pubmed: 29207235
J Chem Phys. 2020 Nov 21;153(19):194101
pubmed: 33218238
Acta Biochim Pol. 2004;51(2):349-71
pubmed: 15218533
Biophys J. 2011 May 4;100(9):L47-9
pubmed: 21539772
J Chem Phys. 2019 Jul 28;151(4):044116
pubmed: 31370528
J Chem Phys. 2008 Jun 28;128(24):244114
pubmed: 18601324
Nat Commun. 2021 Dec 14;12(1):7273
pubmed: 34907176
J Phys Chem B. 2012 Jul 26;116(29):8494-503
pubmed: 22545654
J Chem Phys. 2013 Jul 7;139(1):015102
pubmed: 23822324
J Phys Chem B. 2007 Jul 12;111(27):7812-24
pubmed: 17569554
J Chem Phys. 2021 Apr 28;154(16):164113
pubmed: 33940848
Chem Soc Rev. 2013 Aug 21;42(16):6801-22
pubmed: 23708257
Curr Opin Struct Biol. 2008 Feb;18(1):10-5
pubmed: 18160277