FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308872815> ?p ?o ?g. }

• W4308872815 endingPage "13845" @default.
• W4308872815 startingPage "13845" @default.
• W4308872815 abstract "Kirsten rat sarcoma viral oncogene homolog (KRAS) is a small GTPase protein which plays an important role in the treatment of KRAS mutant cancers. The FDA-approved AMG510 and MRTX849 (phase III clinical trials) are two potent KRASG12C-selective inhibitors that target KRAS G12C. However, the drug resistance caused by the second-site mutation in KRAS has emerged, and the mechanisms of drug resistance at atom level are still unclear. To clarify the mechanisms of drug resistance, we conducted long time molecular dynamics simulations (75 μs in total) to study the structural and energetic features of KRAS G12C and its four drug resistant variants to inhibitors. The combined binding free energy calculation and protein−ligand interaction fingerprint revealed that these second-site mutations indeed caused KRAS to produce different degrees of resistance to AMG510 and MRTX849. Furthermore, Markov State Models and 2D-free energy landscapes analysis revealed the difference in conformational changes of mutated KRAS bound with and without inhibitors. Furthermore, the comparative analysis of these systems showed that there were differences in their allosteric signal pathways. These findings provide the molecular mechanism of drug resistance, which helps to guide novel KRAS G12C inhibitor design to overcome drug resistance." @default.
• W4308872815 created "2022-11-18" @default.
• W4308872815 creator A5017941291 @default.
• W4308872815 creator A5018785079 @default.
• W4308872815 creator A5058215496 @default.
• W4308872815 creator A5058844283 @default.
• W4308872815 creator A5090895839 @default.
• W4308872815 date "2022-11-10" @default.
• W4308872815 modified "2023-10-16" @default.
• W4308872815 title "In Silico Study of the Acquired Resistance Caused by the Secondary Mutations of KRAS G12C Protein Using Long Time Molecular Dynamics Simulation and Markov State Model Analysis" @default.
• W4308872815 cites W1968984443 @default.
• W4308872815 cites W1969836007 @default.
• W4308872815 cites W2016352512 @default.
• W4308872815 cites W2029667189 @default.
• W4308872815 cites W2031843459 @default.
• W4308872815 cites W2055484248 @default.
• W4308872815 cites W2056002345 @default.
• W4308872815 cites W2062410054 @default.
• W4308872815 cites W2065827036 @default.
• W4308872815 cites W2067174909 @default.
• W4308872815 cites W2075369230 @default.
• W4308872815 cites W2081990599 @default.
• W4308872815 cites W2095719702 @default.
• W4308872815 cites W2103631613 @default.
• W4308872815 cites W2106140689 @default.
• W4308872815 cites W2113264508 @default.
• W4308872815 cites W2132629607 @default.
• W4308872815 cites W2142454421 @default.
• W4308872815 cites W2156879354 @default.
• W4308872815 cites W2160858894 @default.
• W4308872815 cites W2226825552 @default.
• W4308872815 cites W2300262456 @default.
• W4308872815 cites W2397367200 @default.
• W4308872815 cites W2501247313 @default.
• W4308872815 cites W2766131649 @default.
• W4308872815 cites W2771729549 @default.
• W4308872815 cites W2783351753 @default.
• W4308872815 cites W2956334136 @default.
• W4308872815 cites W2982321167 @default.
• W4308872815 cites W2993824508 @default.
• W4308872815 cites W2998581726 @default.
• W4308872815 cites W3014882016 @default.
• W4308872815 cites W3034504519 @default.
• W4308872815 cites W3035177263 @default.
• W4308872815 cites W3088730103 @default.
• W4308872815 cites W3142010099 @default.
• W4308872815 cites W3157480760 @default.
• W4308872815 cites W3180296803 @default.
• W4308872815 cites W3196637241 @default.
• W4308872815 cites W3201662252 @default.
• W4308872815 cites W3203735717 @default.
• W4308872815 cites W4200041530 @default.
• W4308872815 cites W4205186273 @default.
• W4308872815 cites W4213177438 @default.
• W4308872815 cites W4213416997 @default.
• W4308872815 cites W4214569871 @default.
• W4308872815 cites W4225592246 @default.
• W4308872815 cites W4230554511 @default.
• W4308872815 cites W4245357560 @default.
• W4308872815 doi "https://doi.org/10.3390/ijms232213845" @default.
• W4308872815 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36430323" @default.
• W4308872815 hasPublicationYear "2022" @default.
• W4308872815 type Work @default.
• W4308872815 citedByCount "1" @default.
• W4308872815 countsByYear W43088728152023 @default.
• W4308872815 crossrefType "journal-article" @default.
• W4308872815 hasAuthorship W4308872815A5017941291 @default.
• W4308872815 hasAuthorship W4308872815A5018785079 @default.
• W4308872815 hasAuthorship W4308872815A5058215496 @default.
• W4308872815 hasAuthorship W4308872815A5058844283 @default.
• W4308872815 hasAuthorship W4308872815A5090895839 @default.
• W4308872815 hasBestOaLocation W43088728151 @default.
• W4308872815 hasConcept C104317684 @default.
• W4308872815 hasConcept C114851261 @default.
• W4308872815 hasConcept C143065580 @default.
• W4308872815 hasConcept C147597530 @default.
• W4308872815 hasConcept C156719811 @default.
• W4308872815 hasConcept C166342909 @default.
• W4308872815 hasConcept C170493617 @default.
• W4308872815 hasConcept C182707283 @default.
• W4308872815 hasConcept C185592680 @default.
• W4308872815 hasConcept C2775905019 @default.
• W4308872815 hasConcept C2780035454 @default.
• W4308872815 hasConcept C2781187634 @default.
• W4308872815 hasConcept C501734568 @default.
• W4308872815 hasConcept C502942594 @default.
• W4308872815 hasConcept C54355233 @default.
• W4308872815 hasConcept C59593255 @default.
• W4308872815 hasConcept C67705224 @default.
• W4308872815 hasConcept C70721500 @default.
• W4308872815 hasConcept C86803240 @default.
• W4308872815 hasConcept C98274493 @default.
• W4308872815 hasConceptScore W4308872815C104317684 @default.
• W4308872815 hasConceptScore W4308872815C114851261 @default.
• W4308872815 hasConceptScore W4308872815C143065580 @default.
• W4308872815 hasConceptScore W4308872815C147597530 @default.
• W4308872815 hasConceptScore W4308872815C156719811 @default.
• W4308872815 hasConceptScore W4308872815C166342909 @default.

• next