FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2086361102> ?p ?o ?g. }

• W2086361102 endingPage "216" @default.
• W2086361102 startingPage "212" @default.
• W2086361102 abstract "The ability to design proteins with high affinity and selectivity for any given small molecule is a rigorous test of our understanding of the physiochemical principles that govern molecular recognition. Attempts to rationally design ligand-binding proteins have met with little success, however, and the computational design of protein-small-molecule interfaces remains an unsolved problem. Current approaches for designing ligand-binding proteins for medical and biotechnological uses rely on raising antibodies against a target antigen in immunized animals and/or performing laboratory-directed evolution of proteins with an existing low affinity for the desired ligand, neither of which allows complete control over the interactions involved in binding. Here we describe a general computational method for designing pre-organized and shape complementary small-molecule-binding sites, and use it to generate protein binders to the steroid digoxigenin (DIG). Of seventeen experimentally characterized designs, two bind DIG; the model of the higher affinity binder has the most energetically favourable and pre-organized interface in the design set. A comprehensive binding-fitness landscape of this design, generated by library selections and deep sequencing, was used to optimize its binding affinity to a picomolar level, and X-ray co-crystal structures of two variants show atomic-level agreement with the corresponding computational models. The optimized binder is selective for DIG over the related steroids digitoxigenin, progesterone and β-oestradiol, and this steroid binding preference can be reprogrammed by manipulation of explicitly designed hydrogen-bonding interactions. The computational design method presented here should enable the development of a new generation of biosensors, therapeutics and diagnostics." @default.
• W2086361102 created "2016-06-24" @default.
• W2086361102 creator A5014064630 @default.
• W2086361102 creator A5028210452 @default.
• W2086361102 creator A5042615663 @default.
• W2086361102 creator A5042937966 @default.
• W2086361102 creator A5051667493 @default.
• W2086361102 creator A5053192926 @default.
• W2086361102 creator A5056661054 @default.
• W2086361102 creator A5060249507 @default.
• W2086361102 creator A5064586384 @default.
• W2086361102 creator A5083192903 @default.
• W2086361102 creator A5085297769 @default.
• W2086361102 date "2013-09-01" @default.
• W2086361102 modified "2023-10-10" @default.
• W2086361102 title "Computational design of ligand-binding proteins with high affinity and selectivity" @default.
• W2086361102 cites W1495758322 @default.
• W2086361102 cites W1515657892 @default.
• W2086361102 cites W1681479328 @default.
• W2086361102 cites W1852517750 @default.
• W2086361102 cites W1982677366 @default.
• W2086361102 cites W1985020303 @default.
• W2086361102 cites W1987696643 @default.
• W2086361102 cites W1996142946 @default.
• W2086361102 cites W2009277434 @default.
• W2086361102 cites W2013789950 @default.
• W2086361102 cites W2015449517 @default.
• W2086361102 cites W2018295245 @default.
• W2086361102 cites W2033969841 @default.
• W2086361102 cites W2042738628 @default.
• W2086361102 cites W2043383780 @default.
• W2086361102 cites W2053937911 @default.
• W2086361102 cites W2056034415 @default.
• W2086361102 cites W2066381187 @default.
• W2086361102 cites W2066962978 @default.
• W2086361102 cites W2073338313 @default.
• W2086361102 cites W2077933693 @default.
• W2086361102 cites W2082260955 @default.
• W2086361102 cites W2084493621 @default.
• W2086361102 cites W2092002806 @default.
• W2086361102 cites W2094136229 @default.
• W2086361102 cites W2107409328 @default.
• W2086361102 cites W2110560814 @default.
• W2086361102 cites W2123850444 @default.
• W2086361102 cites W2129202771 @default.
• W2086361102 cites W2135815512 @default.
• W2086361102 cites W2151887741 @default.
• W2086361102 cites W2153457180 @default.
• W2086361102 cites W2164148151 @default.
• W2086361102 cites W2945068164 @default.
• W2086361102 doi "https://doi.org/10.1038/nature12443" @default.
• W2086361102 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3898436" @default.
• W2086361102 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24005320" @default.
• W2086361102 hasPublicationYear "2013" @default.
• W2086361102 type Work @default.
• W2086361102 sameAs 2086361102 @default.
• W2086361102 citedByCount "351" @default.
• W2086361102 countsByYear W20863611022013 @default.
• W2086361102 countsByYear W20863611022014 @default.
• W2086361102 countsByYear W20863611022015 @default.
• W2086361102 countsByYear W20863611022016 @default.
• W2086361102 countsByYear W20863611022017 @default.
• W2086361102 countsByYear W20863611022018 @default.
• W2086361102 countsByYear W20863611022019 @default.
• W2086361102 countsByYear W20863611022020 @default.
• W2086361102 countsByYear W20863611022021 @default.
• W2086361102 countsByYear W20863611022022 @default.
• W2086361102 countsByYear W20863611022023 @default.
• W2086361102 crossrefType "journal-article" @default.
• W2086361102 hasAuthorship W2086361102A5014064630 @default.
• W2086361102 hasAuthorship W2086361102A5028210452 @default.
• W2086361102 hasAuthorship W2086361102A5042615663 @default.
• W2086361102 hasAuthorship W2086361102A5042937966 @default.
• W2086361102 hasAuthorship W2086361102A5051667493 @default.
• W2086361102 hasAuthorship W2086361102A5053192926 @default.
• W2086361102 hasAuthorship W2086361102A5056661054 @default.
• W2086361102 hasAuthorship W2086361102A5060249507 @default.
• W2086361102 hasAuthorship W2086361102A5064586384 @default.
• W2086361102 hasAuthorship W2086361102A5083192903 @default.
• W2086361102 hasAuthorship W2086361102A5085297769 @default.
• W2086361102 hasBestOaLocation W20863611022 @default.
• W2086361102 hasConcept C104317684 @default.
• W2086361102 hasConcept C107824862 @default.
• W2086361102 hasConcept C109095088 @default.
• W2086361102 hasConcept C116569031 @default.
• W2086361102 hasConcept C150194340 @default.
• W2086361102 hasConcept C152769699 @default.
• W2086361102 hasConcept C161624437 @default.
• W2086361102 hasConcept C16654397 @default.
• W2086361102 hasConcept C170493617 @default.
• W2086361102 hasConcept C185592680 @default.
• W2086361102 hasConcept C204171352 @default.
• W2086361102 hasConcept C2776552150 @default.
• W2086361102 hasConcept C38652104 @default.
• W2086361102 hasConcept C41008148 @default.
• W2086361102 hasConcept C47701112 @default.
• W2086361102 hasConcept C55493867 @default.
• W2086361102 hasConcept C70721500 @default.

• next