Matches in SemOpenAlex for { <https://semopenalex.org/work/W4214851689> ?p ?o ?g. }
Showing items 1 to 95 of
95
with 100 items per page.
- W4214851689 endingPage "11" @default.
- W4214851689 startingPage "1" @default.
- W4214851689 abstract "Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a mitochondrial enzyme that plays an important role in purinecarbon metabolism and thymidine biosynthesis. It has attracted broad interest as a novel therapeutic target for cancer. However, a major problem of current MTHFD2 inhibitors is their lack of selectivity and reactivity with its closest isoform, MTHFD1. Recently, the first selective MTHFD2 inhibitor, DS44960156, has been reported and it exhibits a more than 18-fold selectivity for MTHFD2 over MTHFD1. However, mechanism of DS44960156 selective binding to MTHFD2 over MTHFD1 is unknown. In this study, molecular docking, molecular dynamics (MD) simulations, molecular mechanics generalized born/surface area (MM_GBSA) binding free energy calculations, and analysis of the decomposition of binding free energies were used to investigate the selective binding mechanism of DS44960156 to the folate-binding site of MTHFD2 over MTHFD1. The results revealed that contributions from residues Gln100/Gln132, Val55/Asn87, and Gly237/Gly310 in the binding pocket of MTHFD1/MTHFD2 are the key factors responsible for the binding selectivity. These findings explain the selectivity of DS44960156 to MTHFD2 over MTHFD1, and may provide guidance for the future study and design of novel MTHFD2 inhibitors." @default.
- W4214851689 created "2022-03-05" @default.
- W4214851689 creator A5022652801 @default.
- W4214851689 date "2022-01-01" @default.
- W4214851689 modified "2023-10-01" @default.
- W4214851689 title "Molecular Modeling and Molecular Dynamics Simulation Studies on the Selective Binding Mechanism of MTHFD2 Inhibitors" @default.
- W4214851689 cites W1031578623 @default.
- W4214851689 cites W1983971444 @default.
- W4214851689 cites W2019574809 @default.
- W4214851689 cites W2025116694 @default.
- W4214851689 cites W2063376205 @default.
- W4214851689 cites W2067174909 @default.
- W4214851689 cites W2079372760 @default.
- W4214851689 cites W2103325328 @default.
- W4214851689 cites W2103631613 @default.
- W4214851689 cites W2105103540 @default.
- W4214851689 cites W2128572087 @default.
- W4214851689 cites W2134967712 @default.
- W4214851689 cites W2142868265 @default.
- W4214851689 cites W2147993766 @default.
- W4214851689 cites W2148893085 @default.
- W4214851689 cites W2168735777 @default.
- W4214851689 cites W2179581654 @default.
- W4214851689 cites W2279293113 @default.
- W4214851689 cites W2325034207 @default.
- W4214851689 cites W2405069786 @default.
- W4214851689 cites W2470899874 @default.
- W4214851689 cites W2557844588 @default.
- W4214851689 cites W2768015497 @default.
- W4214851689 cites W2782093867 @default.
- W4214851689 cites W2903973932 @default.
- W4214851689 cites W2918075062 @default.
- W4214851689 cites W2944993968 @default.
- W4214851689 doi "https://doi.org/10.4236/cmb.2022.121001" @default.
- W4214851689 hasPublicationYear "2022" @default.
- W4214851689 type Work @default.
- W4214851689 citedByCount "1" @default.
- W4214851689 countsByYear W42148516892023 @default.
- W4214851689 crossrefType "journal-article" @default.
- W4214851689 hasAuthorship W4214851689A5022652801 @default.
- W4214851689 hasBestOaLocation W42148516891 @default.
- W4214851689 hasConcept C107824862 @default.
- W4214851689 hasConcept C118792377 @default.
- W4214851689 hasConcept C121332964 @default.
- W4214851689 hasConcept C12554922 @default.
- W4214851689 hasConcept C147597530 @default.
- W4214851689 hasConcept C159110408 @default.
- W4214851689 hasConcept C161790260 @default.
- W4214851689 hasConcept C185544564 @default.
- W4214851689 hasConcept C185592680 @default.
- W4214851689 hasConcept C25057246 @default.
- W4214851689 hasConcept C41685203 @default.
- W4214851689 hasConcept C55493867 @default.
- W4214851689 hasConcept C59593255 @default.
- W4214851689 hasConcept C71240020 @default.
- W4214851689 hasConcept C71924100 @default.
- W4214851689 hasConcept C86803240 @default.
- W4214851689 hasConcept C93282013 @default.
- W4214851689 hasConceptScore W4214851689C107824862 @default.
- W4214851689 hasConceptScore W4214851689C118792377 @default.
- W4214851689 hasConceptScore W4214851689C121332964 @default.
- W4214851689 hasConceptScore W4214851689C12554922 @default.
- W4214851689 hasConceptScore W4214851689C147597530 @default.
- W4214851689 hasConceptScore W4214851689C159110408 @default.
- W4214851689 hasConceptScore W4214851689C161790260 @default.
- W4214851689 hasConceptScore W4214851689C185544564 @default.
- W4214851689 hasConceptScore W4214851689C185592680 @default.
- W4214851689 hasConceptScore W4214851689C25057246 @default.
- W4214851689 hasConceptScore W4214851689C41685203 @default.
- W4214851689 hasConceptScore W4214851689C55493867 @default.
- W4214851689 hasConceptScore W4214851689C59593255 @default.
- W4214851689 hasConceptScore W4214851689C71240020 @default.
- W4214851689 hasConceptScore W4214851689C71924100 @default.
- W4214851689 hasConceptScore W4214851689C86803240 @default.
- W4214851689 hasConceptScore W4214851689C93282013 @default.
- W4214851689 hasIssue "01" @default.
- W4214851689 hasLocation W42148516891 @default.
- W4214851689 hasOpenAccess W4214851689 @default.
- W4214851689 hasPrimaryLocation W42148516891 @default.
- W4214851689 hasRelatedWork W1980097204 @default.
- W4214851689 hasRelatedWork W2033451818 @default.
- W4214851689 hasRelatedWork W2061470146 @default.
- W4214851689 hasRelatedWork W2170354954 @default.
- W4214851689 hasRelatedWork W2605347687 @default.
- W4214851689 hasRelatedWork W2763518371 @default.
- W4214851689 hasRelatedWork W3136898766 @default.
- W4214851689 hasRelatedWork W3165202486 @default.
- W4214851689 hasRelatedWork W4283775951 @default.
- W4214851689 hasRelatedWork W4379196658 @default.
- W4214851689 hasVolume "12" @default.
- W4214851689 isParatext "false" @default.
- W4214851689 isRetracted "false" @default.
- W4214851689 workType "article" @default.