Matches in SemOpenAlex for { <https://semopenalex.org/work/W2519157074> ?p ?o ?g. }
- W2519157074 endingPage "991" @default.
- W2519157074 startingPage "975" @default.
- W2519157074 abstract "Understanding subtle aspects of hydrogen bonding is a challenging but crucial task to improve our ability to design ligands with high affinity for protein hosts. To gain a deeper understanding of these aspects, we investigated a series of thrombin inhibitors in which the basicity of the ligand's group that accepts an H-bond from Gly216 was modulated via bioisosterism; e.g., a C=O acceptor was made electron deficient or rich via bioisosteric replacements of the adjacent moiety. Although the ligand's binding affinity was anticipated to improve when the H-bond basicity is increased (due to stronger H-bonding with the protein), we herein present data that unexpectedly revealed an opposite trend. This trend was attributed to a dominating role played by desolvation in determining the relative binding affinity. For example, a decrease in the H-bond basicity reduces the desolvation penalty and, as experimentally observed, improves the binding affinity, given that the reduction in the desolvation penalty dominates the change in the net contribution of the ligand's interactions with the protein. The current study, therefore, reveals that desolvation can be a major underlying cause for the apparently counterintuitive structure-activity relationship (SAR) outcomes, and indicates that understanding this factor can improve our ability to predict binding affinity and to design more potent ligands." @default.
- W2519157074 created "2016-09-23" @default.
- W2519157074 creator A5016700895 @default.
- W2519157074 creator A5071964348 @default.
- W2519157074 creator A5079698696 @default.
- W2519157074 date "2017-01-01" @default.
- W2519157074 modified "2023-09-23" @default.
- W2519157074 title "Modulating hydrogen-bond basicity within the context of protein-ligand binding: A case study with thrombin inhibitors that reveals a dominating role for desolvation" @default.
- W2519157074 cites W1603151790 @default.
- W2519157074 cites W1967004474 @default.
- W2519157074 cites W1971911697 @default.
- W2519157074 cites W1974818478 @default.
- W2519157074 cites W1975298181 @default.
- W2519157074 cites W1975947882 @default.
- W2519157074 cites W1980249106 @default.
- W2519157074 cites W1980337077 @default.
- W2519157074 cites W1988883534 @default.
- W2519157074 cites W1991954272 @default.
- W2519157074 cites W2004868986 @default.
- W2519157074 cites W2007765234 @default.
- W2519157074 cites W2021693516 @default.
- W2519157074 cites W2023271753 @default.
- W2519157074 cites W2032525140 @default.
- W2519157074 cites W2034585379 @default.
- W2519157074 cites W2035755017 @default.
- W2519157074 cites W2046412723 @default.
- W2519157074 cites W2046634819 @default.
- W2519157074 cites W2054582528 @default.
- W2519157074 cites W2055903184 @default.
- W2519157074 cites W2061304828 @default.
- W2519157074 cites W2062299665 @default.
- W2519157074 cites W2072557214 @default.
- W2519157074 cites W2074631079 @default.
- W2519157074 cites W2076227819 @default.
- W2519157074 cites W2079991727 @default.
- W2519157074 cites W2085313140 @default.
- W2519157074 cites W2093938060 @default.
- W2519157074 cites W2098376669 @default.
- W2519157074 cites W2122784237 @default.
- W2519157074 cites W2124882231 @default.
- W2519157074 cites W2127336290 @default.
- W2519157074 cites W2130166312 @default.
- W2519157074 cites W2148284063 @default.
- W2519157074 cites W2151744400 @default.
- W2519157074 cites W2155358697 @default.
- W2519157074 cites W2170660770 @default.
- W2519157074 cites W2323821840 @default.
- W2519157074 cites W2461667630 @default.
- W2519157074 cites W2952489168 @default.
- W2519157074 cites W4254110724 @default.
- W2519157074 cites W953510588 @default.
- W2519157074 cites W2046912862 @default.
- W2519157074 doi "https://doi.org/10.1016/j.ejmech.2016.09.038" @default.
- W2519157074 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27816890" @default.
- W2519157074 hasPublicationYear "2017" @default.
- W2519157074 type Work @default.
- W2519157074 sameAs 2519157074 @default.
- W2519157074 citedByCount "6" @default.
- W2519157074 countsByYear W25191570742017 @default.
- W2519157074 countsByYear W25191570742018 @default.
- W2519157074 countsByYear W25191570742020 @default.
- W2519157074 countsByYear W25191570742021 @default.
- W2519157074 countsByYear W25191570742022 @default.
- W2519157074 crossrefType "journal-article" @default.
- W2519157074 hasAuthorship W2519157074A5016700895 @default.
- W2519157074 hasAuthorship W2519157074A5071964348 @default.
- W2519157074 hasAuthorship W2519157074A5079698696 @default.
- W2519157074 hasConcept C112887158 @default.
- W2519157074 hasConcept C116569031 @default.
- W2519157074 hasConcept C147597530 @default.
- W2519157074 hasConcept C151730666 @default.
- W2519157074 hasConcept C170493617 @default.
- W2519157074 hasConcept C178790620 @default.
- W2519157074 hasConcept C185592680 @default.
- W2519157074 hasConcept C2779343474 @default.
- W2519157074 hasConcept C32909587 @default.
- W2519157074 hasConcept C55493867 @default.
- W2519157074 hasConcept C71240020 @default.
- W2519157074 hasConcept C86803240 @default.
- W2519157074 hasConceptScore W2519157074C112887158 @default.
- W2519157074 hasConceptScore W2519157074C116569031 @default.
- W2519157074 hasConceptScore W2519157074C147597530 @default.
- W2519157074 hasConceptScore W2519157074C151730666 @default.
- W2519157074 hasConceptScore W2519157074C170493617 @default.
- W2519157074 hasConceptScore W2519157074C178790620 @default.
- W2519157074 hasConceptScore W2519157074C185592680 @default.
- W2519157074 hasConceptScore W2519157074C2779343474 @default.
- W2519157074 hasConceptScore W2519157074C32909587 @default.
- W2519157074 hasConceptScore W2519157074C55493867 @default.
- W2519157074 hasConceptScore W2519157074C71240020 @default.
- W2519157074 hasConceptScore W2519157074C86803240 @default.
- W2519157074 hasLocation W25191570741 @default.
- W2519157074 hasLocation W25191570742 @default.
- W2519157074 hasOpenAccess W2519157074 @default.
- W2519157074 hasPrimaryLocation W25191570741 @default.
- W2519157074 hasRelatedWork W1969940393 @default.
- W2519157074 hasRelatedWork W2011802865 @default.
- W2519157074 hasRelatedWork W2034135491 @default.