FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387661570> ?p ?o ?g. }

• W4387661570 abstract "Phosphatase and tensin homolog (PTEN), a tumor suppressor with dual phosphatase properties, is a key factor in PI3K/AKT signaling pathway. Pathogenic germline variation in PTEN can abrogate its ability to dephosphorylate, causing high cancer risk. Lack of functional evidence lets numerous PTEN variants be classified as variants of uncertain significance (VUS). Utilizing Molecular Dynamics (MD) simulations, we performed a thorough evaluation for 147 PTEN missense VUS, sorting them into 66 deleterious and 81 tolerated variants. Utilizing replica exchange molecular dynamic (REMD) simulations, we further assessed the variants situated in the catalytic core of PTEN's phosphatase domain and uncovered conformational alterations influencing the structural stability of the phosphatase domain. There was a high degree of agreement between our results and the variants classified by Variant Abundance by Massively Parallel Sequencing, saturation mutagenesis, multiplexed functional data and experimental assays. Our extensive analysis of PTEN missense VUS should benefit their clinical applications in PTEN-related cancer.Classification of PTEN variants affecting its lipid phosphatase activity is important for understanding the roles of PTEN variation in the pathogenesis of hereditary and sporadic malignancies. Of the 3000 variants identified in PTEN, 1296 (43%) were assigned as VUS. Here, we applied MD and REMD simulations to investigate the effects of PTEN missense VUS on the structural integrity of the PTEN phosphatase domain consisting the WPD, P and TI active sites. We classified a total of 147 missense VUS into 66 deleterious and 81 tolerated variants by referring to the control group comprising 54 pathogenic and 12 benign variants. The classification was largely in concordance with these classified by experimental approaches." @default.
• W4387661570 created "2023-10-17" @default.
• W4387661570 creator A5001797437 @default.
• W4387661570 creator A5032330103 @default.
• W4387661570 creator A5038179826 @default.
• W4387661570 creator A5052510573 @default.
• W4387661570 date "2023-09-22" @default.
• W4387661570 modified "2023-10-17" @default.
• W4387661570 title "Classification of PTEN missense VUS through exascale simulations" @default.
• W4387661570 cites W1031578623 @default.
• W4387661570 cites W1939083266 @default.
• W4387661570 cites W1964128675 @default.
• W4387661570 cites W1966078827 @default.
• W4387661570 cites W1968955881 @default.
• W4387661570 cites W1970413157 @default.
• W4387661570 cites W1981021420 @default.
• W4387661570 cites W1983845790 @default.
• W4387661570 cites W1998038367 @default.
• W4387661570 cites W2000093333 @default.
• W4387661570 cites W2001413092 @default.
• W4387661570 cites W2006617902 @default.
• W4387661570 cites W2016267980 @default.
• W4387661570 cites W2020697273 @default.
• W4387661570 cites W2032363535 @default.
• W4387661570 cites W2035266068 @default.
• W4387661570 cites W2039514112 @default.
• W4387661570 cites W2068345721 @default.
• W4387661570 cites W2071590886 @default.
• W4387661570 cites W2076457965 @default.
• W4387661570 cites W2081693079 @default.
• W4387661570 cites W2085986834 @default.
• W4387661570 cites W2100833559 @default.
• W4387661570 cites W2101671848 @default.
• W4387661570 cites W2110335151 @default.
• W4387661570 cites W2111125738 @default.
• W4387661570 cites W2121637291 @default.
• W4387661570 cites W2154915448 @default.
• W4387661570 cites W2156084923 @default.
• W4387661570 cites W2159957100 @default.
• W4387661570 cites W2161810908 @default.
• W4387661570 cites W2163673534 @default.
• W4387661570 cites W2165516672 @default.
• W4387661570 cites W2195303995 @default.
• W4387661570 cites W2376573086 @default.
• W4387661570 cites W2770026599 @default.
• W4387661570 cites W2788783025 @default.
• W4387661570 cites W2794121543 @default.
• W4387661570 cites W2805276936 @default.
• W4387661570 cites W2885278423 @default.
• W4387661570 cites W2950629294 @default.
• W4387661570 cites W2994879846 @default.
• W4387661570 cites W2999871199 @default.
• W4387661570 cites W3000533753 @default.
• W4387661570 cites W3012594289 @default.
• W4387661570 cites W3083406432 @default.
• W4387661570 cites W3110494028 @default.
• W4387661570 cites W3177828909 @default.
• W4387661570 cites W3205136345 @default.
• W4387661570 cites W3213536168 @default.
• W4387661570 cites W4213031026 @default.
• W4387661570 cites W4213150904 @default.
• W4387661570 cites W4225161546 @default.
• W4387661570 cites W4251751280 @default.
• W4387661570 cites W4318955131 @default.
• W4387661570 cites W4321373243 @default.
• W4387661570 doi "https://doi.org/10.1093/bib/bbad361" @default.
• W4387661570 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37843401" @default.
• W4387661570 hasPublicationYear "2023" @default.
• W4387661570 type Work @default.
• W4387661570 citedByCount "0" @default.
• W4387661570 crossrefType "journal-article" @default.
• W4387661570 hasAuthorship W4387661570A5001797437 @default.
• W4387661570 hasAuthorship W4387661570A5032330103 @default.
• W4387661570 hasAuthorship W4387661570A5038179826 @default.
• W4387661570 hasAuthorship W4387661570A5052510573 @default.
• W4387661570 hasConcept C104317684 @default.
• W4387661570 hasConcept C109825262 @default.
• W4387661570 hasConcept C11960822 @default.
• W4387661570 hasConcept C178666793 @default.
• W4387661570 hasConcept C2777609662 @default.
• W4387661570 hasConcept C2779549131 @default.
• W4387661570 hasConcept C501734568 @default.
• W4387661570 hasConcept C502942594 @default.
• W4387661570 hasConcept C54355233 @default.
• W4387661570 hasConcept C62478195 @default.
• W4387661570 hasConcept C70721500 @default.
• W4387661570 hasConcept C75563809 @default.
• W4387661570 hasConcept C86554907 @default.
• W4387661570 hasConcept C86803240 @default.
• W4387661570 hasConceptScore W4387661570C104317684 @default.
• W4387661570 hasConceptScore W4387661570C109825262 @default.
• W4387661570 hasConceptScore W4387661570C11960822 @default.
• W4387661570 hasConceptScore W4387661570C178666793 @default.
• W4387661570 hasConceptScore W4387661570C2777609662 @default.
• W4387661570 hasConceptScore W4387661570C2779549131 @default.
• W4387661570 hasConceptScore W4387661570C501734568 @default.
• W4387661570 hasConceptScore W4387661570C502942594 @default.
• W4387661570 hasConceptScore W4387661570C54355233 @default.
• W4387661570 hasConceptScore W4387661570C62478195 @default.
• W4387661570 hasConceptScore W4387661570C70721500 @default.

• next