A topological data analytic approach for discovering biophysical signatures in protein dynamics.
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
31
08
2021
accepted:
22
03
2022
revised:
12
05
2022
pubmed:
3
5
2022
medline:
18
5
2022
entrez:
2
5
2022
Statut:
epublish
Résumé
Identifying structural differences among proteins can be a non-trivial task. When contrasting ensembles of protein structures obtained from molecular dynamics simulations, biologically-relevant features can be easily overshadowed by spurious fluctuations. Here, we present SINATRA Pro, a computational pipeline designed to robustly identify topological differences between two sets of protein structures. Algorithmically, SINATRA Pro works by first taking in the 3D atomic coordinates for each protein snapshot and summarizing them according to their underlying topology. Statistically significant topological features are then projected back onto a user-selected representative protein structure, thus facilitating the visual identification of biophysical signatures of different protein ensembles. We assess the ability of SINATRA Pro to detect minute conformational changes in five independent protein systems of varying complexities. In all test cases, SINATRA Pro identifies known structural features that have been validated by previous experimental and computational studies, as well as novel features that are also likely to be biologically-relevant according to the literature. These results highlight SINATRA Pro as a promising method for facilitating the non-trivial task of pattern recognition in trajectories resulting from molecular dynamics simulations, with substantially increased resolution.
Identifiants
pubmed: 35500014
doi: 10.1371/journal.pcbi.1010045
pii: PCOMPBIOL-D-21-01589
pmc: PMC9098046
doi:
Substances chimiques
Proteins
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010045Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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