FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313894736> ?p ?o ?g. }

• W4313894736 abstract "In response to antibiotics that inhibit a bacterial enzyme, resistance mutations inevitably arise. Predicting them ahead of time would aid target selection and drug design. The simplest resistance mechanism would be to reduce antibiotic binding without sacrificing too much substrate binding. The property that reflects this is the enzyme “vitality”, defined here as the difference between the inhibitor and substrate binding free energies. To predict such mutations, we borrow methodology from computational protein design. We use a Monte Carlo exploration of mutation space and vitality changes, allowing us to rank thousands of mutations and identify ones that might provide resistance through the simple mechanism considered. As an illustration, we chose dihydrofolate reductase, an essential enzyme targeted by several antibiotics. We simulated its complexes with the inhibitor trimethoprim and the substrate dihydrofolate. 20 active site positions were mutated, or “redesigned” individually, then in pairs or quartets. We computed the resulting binding free energy and vitality changes. Out of seven known resistance mutations involving active site positions, five were correctly recovered. Ten positions exhibited mutations with significant predicted vitality gains. Direct couplings between designed positions were predicted to be small, which reduces the combinatorial complexity of the mutation space to be explored. It also suggests that over the course of evolution, resistance mutations involving several positions do not need the underlying point mutations to arise all at once: they can appear and become fixed one after the other." @default.
• W4313894736 created "2023-01-10" @default.
• W4313894736 creator A5028177049 @default.
• W4313894736 creator A5033410644 @default.
• W4313894736 creator A5065006700 @default.
• W4313894736 creator A5068360547 @default.
• W4313894736 date "2023-01-09" @default.
• W4313894736 modified "2023-10-18" @default.
• W4313894736 title "Computational protein design repurposed to explore enzyme vitality and help predict antibiotic resistance" @default.
• W4313894736 cites W1976499671 @default.
• W4313894736 cites W1992739911 @default.
• W4313894736 cites W1997844736 @default.
• W4313894736 cites W1998419944 @default.
• W4313894736 cites W2018082367 @default.
• W4313894736 cites W2019691224 @default.
• W4313894736 cites W2038758364 @default.
• W4313894736 cites W2067174909 @default.
• W4313894736 cites W2102388964 @default.
• W4313894736 cites W2108250754 @default.
• W4313894736 cites W2122199548 @default.
• W4313894736 cites W2126559590 @default.
• W4313894736 cites W2133718756 @default.
• W4313894736 cites W2144794655 @default.
• W4313894736 cites W2150981663 @default.
• W4313894736 cites W2482253982 @default.
• W4313894736 cites W2606202207 @default.
• W4313894736 cites W2640270266 @default.
• W4313894736 cites W2743553234 @default.
• W4313894736 cites W2751609738 @default.
• W4313894736 cites W2802643187 @default.
• W4313894736 cites W2944245644 @default.
• W4313894736 cites W2999166706 @default.
• W4313894736 cites W3044941661 @default.
• W4313894736 cites W3098122596 @default.
• W4313894736 cites W3100163799 @default.
• W4313894736 cites W3101977221 @default.
• W4313894736 cites W3162660302 @default.
• W4313894736 cites W3198493470 @default.
• W4313894736 doi "https://doi.org/10.3389/fmolb.2022.905588" @default.
• W4313894736 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36699702" @default.
• W4313894736 hasPublicationYear "2023" @default.
• W4313894736 type Work @default.
• W4313894736 citedByCount "1" @default.
• W4313894736 countsByYear W43138947362023 @default.
• W4313894736 crossrefType "journal-article" @default.
• W4313894736 hasAuthorship W4313894736A5028177049 @default.
• W4313894736 hasAuthorship W4313894736A5033410644 @default.
• W4313894736 hasAuthorship W4313894736A5065006700 @default.
• W4313894736 hasAuthorship W4313894736A5068360547 @default.
• W4313894736 hasBestOaLocation W43138947361 @default.
• W4313894736 hasConcept C104317684 @default.
• W4313894736 hasConcept C107824862 @default.
• W4313894736 hasConcept C114851261 @default.
• W4313894736 hasConcept C143065580 @default.
• W4313894736 hasConcept C176944494 @default.
• W4313894736 hasConcept C181199279 @default.
• W4313894736 hasConcept C185592680 @default.
• W4313894736 hasConcept C18903297 @default.
• W4313894736 hasConcept C2777289219 @default.
• W4313894736 hasConcept C2779829227 @default.
• W4313894736 hasConcept C2781320022 @default.
• W4313894736 hasConcept C501593827 @default.
• W4313894736 hasConcept C501734568 @default.
• W4313894736 hasConcept C54355233 @default.
• W4313894736 hasConcept C55493867 @default.
• W4313894736 hasConcept C70721500 @default.
• W4313894736 hasConcept C86803240 @default.
• W4313894736 hasConceptScore W4313894736C104317684 @default.
• W4313894736 hasConceptScore W4313894736C107824862 @default.
• W4313894736 hasConceptScore W4313894736C114851261 @default.
• W4313894736 hasConceptScore W4313894736C143065580 @default.
• W4313894736 hasConceptScore W4313894736C176944494 @default.
• W4313894736 hasConceptScore W4313894736C181199279 @default.
• W4313894736 hasConceptScore W4313894736C185592680 @default.
• W4313894736 hasConceptScore W4313894736C18903297 @default.
• W4313894736 hasConceptScore W4313894736C2777289219 @default.
• W4313894736 hasConceptScore W4313894736C2779829227 @default.
• W4313894736 hasConceptScore W4313894736C2781320022 @default.
• W4313894736 hasConceptScore W4313894736C501593827 @default.
• W4313894736 hasConceptScore W4313894736C501734568 @default.
• W4313894736 hasConceptScore W4313894736C54355233 @default.
• W4313894736 hasConceptScore W4313894736C55493867 @default.
• W4313894736 hasConceptScore W4313894736C70721500 @default.
• W4313894736 hasConceptScore W4313894736C86803240 @default.
• W4313894736 hasLocation W43138947361 @default.
• W4313894736 hasLocation W43138947362 @default.
• W4313894736 hasLocation W43138947363 @default.
• W4313894736 hasLocation W43138947364 @default.
• W4313894736 hasOpenAccess W4313894736 @default.
• W4313894736 hasPrimaryLocation W43138947361 @default.
• W4313894736 hasRelatedWork W101124211 @default.
• W4313894736 hasRelatedWork W1978844459 @default.
• W4313894736 hasRelatedWork W2009647017 @default.
• W4313894736 hasRelatedWork W2028961943 @default.
• W4313894736 hasRelatedWork W2031846255 @default.
• W4313894736 hasRelatedWork W2073288950 @default.
• W4313894736 hasRelatedWork W2125255347 @default.
• W4313894736 hasRelatedWork W2184528438 @default.
• W4313894736 hasRelatedWork W2391633642 @default.
• W4313894736 hasRelatedWork W4248490988 @default.

• next