Fewer Dimensions, More Structures for Improved Discrete Models of Dynamics of Free versus Antigen-Bound Antibody.
Markov State Model
antibody
antigen binding
molecular dynamics
structure
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
21 07 2022
21 07 2022
Historique:
received:
31
05
2022
revised:
12
07
2022
accepted:
19
07
2022
entrez:
27
7
2022
pubmed:
28
7
2022
medline:
29
7
2022
Statut:
epublish
Résumé
Over the past decade, Markov State Models (MSM) have emerged as powerful methodologies to build discrete models of dynamics over structures obtained from Molecular Dynamics trajectories. The identification of macrostates for the MSM is a central decision that impacts the quality of the MSM but depends on both the selected representation of a structure and the clustering algorithm utilized over the featurized structures. Motivated by a large molecular system in its free and bound state, this paper investigates two directions of research, further reducing the representation dimensionality in a non-parametric, data-driven manner and including more structures in the computation. Rigorous evaluation of the quality of obtained MSMs via various statistical tests in a comparative setting firmly shows that fewer dimensions and more structures result in a better MSM. Many interesting findings emerge from the best MSM, advancing our understanding of the relationship between antibody dynamics and antibody-antigen recognition.
Identifiants
pubmed: 35883567
pii: biom12071011
doi: 10.3390/biom12071011
pmc: PMC9313177
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : HHSN261201500003I
Pays : United States
Références
PLoS One. 2014 Mar 26;9(3):e92870
pubmed: 24671209
J Bioinform Comput Biol. 2019 Dec;17(6):1940014
pubmed: 32019409
Nature. 2021 Aug;596(7873):590-596
pubmed: 34293799
Nat Chem. 2017 Oct;9(10):1005-1011
pubmed: 28937668
Proc Natl Acad Sci U S A. 2013 May 28;110(22):9019-24
pubmed: 23661056
J Biol Chem. 2008 Nov 14;283(46):31366-70
pubmed: 18806257
Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8131-8136
pubmed: 30975755
J Chem Phys. 2009 Sep 28;131(12):124101
pubmed: 19791846
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):388-97
pubmed: 23519414
Front Immunol. 2013 Oct 08;4:302
pubmed: 24115948
Molecules. 2018 Jan 19;23(1):
pubmed: 29351266
Protein Sci. 2003 Oct;12(10):2125-31
pubmed: 14500870
PLoS Comput Biol. 2016 Apr 28;12(4):e1004619
pubmed: 27124275
ACS Chem Neurosci. 2020 Oct 21;11(20):3233-3244
pubmed: 32991803
Mol Immunol. 2010 Apr;47(7-8):1421-5
pubmed: 20299100
J Chem Phys. 2011 May 7;134(17):174105
pubmed: 21548671
Biochemistry. 2008 Jul 8;47(27):7237-47
pubmed: 18549243
Nat Commun. 2015 Jul 02;6:7653
pubmed: 26134632
Antibodies (Basel). 2018 Jun 07;7(2):
pubmed: 31544872
J Am Chem Soc. 2018 Feb 21;140(7):2386-2396
pubmed: 29323881
J Chem Theory Comput. 2014 Jul 8;10(7):2648-2657
pubmed: 25473382
J Clin Invest. 1996 Nov 15;98(10):2235-43
pubmed: 8941639
MAbs. 2019 Jan;11(1):58-74
pubmed: 30212263
J Biol Chem. 2012 Oct 12;287(42):35409-35417
pubmed: 22930758
PLoS One. 2009;4(4):e5392
pubmed: 19399183
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12680-5
pubmed: 22723360
Molecules. 2019 Feb 28;24(5):
pubmed: 30823390
Biophys J. 2017 Jan 10;112(1):10-15
pubmed: 28076801
Biochemistry. 1991 Jul 2;30(26):6604-10
pubmed: 2054358
Methods. 2010 Sep;52(1):99-105
pubmed: 20570730
J Immunol. 1993 Mar 15;150(6):2231-42
pubmed: 7680687
J Chem Theory Comput. 2013 Apr 9;9(4):2000-2009
pubmed: 23750122
PLoS Comput Biol. 2015 Jul 01;11(7):e1004327
pubmed: 26132144
Biomolecules. 2019 Oct 14;9(10):
pubmed: 31615116
Anal Biochem. 2022 Mar 1;640:114411
pubmed: 34648807
BMC Struct Biol. 2007 May 17;7:31
pubmed: 17509130
BMC Struct Biol. 2013;13 Suppl 1:S8
pubmed: 24565158
J Comput Chem. 2007 Jul 30;28(10):1711-23
pubmed: 17342716
J Comput Chem. 2013 Sep 30;34(25):2135-45
pubmed: 23832629
Bioinformatics. 2017 Apr 1;33(7):997-1004
pubmed: 28062450
Curr Opin Struct Biol. 2014 Apr;25:135-44
pubmed: 24836551
Front Microbiol. 2016 Feb 04;7:22
pubmed: 26870003
BMC Bioinformatics. 2020 Dec 9;21(Suppl 1):189
pubmed: 33297949
Molecules. 2020 May 09;25(9):
pubmed: 32397410
J Chem Theory Comput. 2012 Jul 10;8(7):2223-38
pubmed: 26588955
J Immunol. 2005 Feb 15;174(4):2132-42
pubmed: 15699144
J Chem Theory Comput. 2015 Nov 10;11(11):5525-42
pubmed: 26574340