Matches in SemOpenAlex for { <https://semopenalex.org/work/W2056006593> ?p ?o ?g. }
- W2056006593 endingPage "13068" @default.
- W2056006593 startingPage "13058" @default.
- W2056006593 abstract "Hemoglobin is a complex system that undergoes conformational changes in response to oxygen, allosteric effectors, mutations, and environmental changes. Here, we study allostery and polymerization of hemoglobin and its variants by application of two previously described methods: (i) AllosMod for simulating allostery dynamics given two allosterically related input structures and (ii) a machine-learning method for dynamics- and structure-based prediction of the mutation impact on allostery (Weinkam et al. J. Mol. Biol. 2013, 425, 647–661), now applicable to systems with multiple coupled binding sites, such as hemoglobin. First, we predict the relative stabilities of substates and microstates of hemoglobin, which are determined primarily by entropy within our model. Next, we predict the impact of 866 annotated mutations on hemoglobin’s oxygen binding equilibrium. We then discuss a subset of 30 mutations that occur in the presence of the sickle cell mutation and whose effects on polymerization have been measured. Seven of these HbS mutations occur in three predicted druggable binding pockets that might be exploited to directly inhibit polymerization; one of these binding pockets is not apparent in the crystal structure, but only in structures generated by AllosMod. For the 30 mutations, we predict that mutation-induced conformational changes within a single tetramer tend not to significantly impact polymerization; instead, these mutations more likely impact polymerization by directly perturbing a polymerization interface. Finally, our analysis of allostery allows us to hypothesize why hemoglobin evolved to have multiple subunits and a persistent low frequency sickle cell mutation." @default.
- W2056006593 created "2016-06-24" @default.
- W2056006593 creator A5028845140 @default.
- W2056006593 creator A5030413988 @default.
- W2056006593 date "2013-09-09" @default.
- W2056006593 modified "2023-10-18" @default.
- W2056006593 title "Mapping Polymerization and Allostery of Hemoglobin S Using Point Mutations" @default.
- W2056006593 cites W1535994913 @default.
- W2056006593 cites W1837550175 @default.
- W2056006593 cites W1968165696 @default.
- W2056006593 cites W1972919297 @default.
- W2056006593 cites W1974617804 @default.
- W2056006593 cites W1980262534 @default.
- W2056006593 cites W1980885156 @default.
- W2056006593 cites W1983697172 @default.
- W2056006593 cites W1983979304 @default.
- W2056006593 cites W1998093640 @default.
- W2056006593 cites W2000567066 @default.
- W2056006593 cites W2000690605 @default.
- W2056006593 cites W2002481233 @default.
- W2056006593 cites W2002542088 @default.
- W2056006593 cites W2003271897 @default.
- W2056006593 cites W2005392755 @default.
- W2056006593 cites W2014038272 @default.
- W2056006593 cites W2017992198 @default.
- W2056006593 cites W2024105622 @default.
- W2056006593 cites W2024342693 @default.
- W2056006593 cites W2024912628 @default.
- W2056006593 cites W2025157802 @default.
- W2056006593 cites W2026911129 @default.
- W2056006593 cites W2027816595 @default.
- W2056006593 cites W2028226298 @default.
- W2056006593 cites W2030368884 @default.
- W2056006593 cites W2033232950 @default.
- W2056006593 cites W2033711351 @default.
- W2056006593 cites W2039517095 @default.
- W2056006593 cites W2042964041 @default.
- W2056006593 cites W2043141532 @default.
- W2056006593 cites W2043580883 @default.
- W2056006593 cites W2044833353 @default.
- W2056006593 cites W2044882887 @default.
- W2056006593 cites W2045741754 @default.
- W2056006593 cites W2049129790 @default.
- W2056006593 cites W2054762683 @default.
- W2056006593 cites W2059852102 @default.
- W2056006593 cites W2061865181 @default.
- W2056006593 cites W2063485848 @default.
- W2056006593 cites W2067823673 @default.
- W2056006593 cites W2070783701 @default.
- W2056006593 cites W2071075252 @default.
- W2056006593 cites W2071686464 @default.
- W2056006593 cites W2084565056 @default.
- W2056006593 cites W2085928981 @default.
- W2056006593 cites W2089541065 @default.
- W2056006593 cites W2089694825 @default.
- W2056006593 cites W2089750168 @default.
- W2056006593 cites W2094795801 @default.
- W2056006593 cites W2106531843 @default.
- W2056006593 cites W2109356155 @default.
- W2056006593 cites W2115152262 @default.
- W2056006593 cites W2116695133 @default.
- W2056006593 cites W2118733486 @default.
- W2056006593 cites W2119200232 @default.
- W2056006593 cites W2122484762 @default.
- W2056006593 cites W2128855640 @default.
- W2056006593 cites W2133760429 @default.
- W2056006593 cites W2134742468 @default.
- W2056006593 cites W2136238731 @default.
- W2056006593 cites W2140565568 @default.
- W2056006593 cites W2142379241 @default.
- W2056006593 cites W2145498345 @default.
- W2056006593 cites W2147466870 @default.
- W2056006593 cites W2148634928 @default.
- W2056006593 cites W2157605186 @default.
- W2056006593 cites W2158076215 @default.
- W2056006593 cites W2160349767 @default.
- W2056006593 cites W2164088236 @default.
- W2056006593 cites W3103106181 @default.
- W2056006593 cites W4236120028 @default.
- W2056006593 doi "https://doi.org/10.1021/jp4025156" @default.
- W2056006593 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3973026" @default.
- W2056006593 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23957820" @default.
- W2056006593 hasPublicationYear "2013" @default.
- W2056006593 type Work @default.
- W2056006593 sameAs 2056006593 @default.
- W2056006593 citedByCount "3" @default.
- W2056006593 countsByYear W20560065932014 @default.
- W2056006593 crossrefType "journal-article" @default.
- W2056006593 hasAuthorship W2056006593A5028845140 @default.
- W2056006593 hasAuthorship W2056006593A5030413988 @default.
- W2056006593 hasBestOaLocation W20560065932 @default.
- W2056006593 hasConcept C104317684 @default.
- W2056006593 hasConcept C12554922 @default.
- W2056006593 hasConcept C166342909 @default.
- W2056006593 hasConcept C170493617 @default.
- W2056006593 hasConcept C176944494 @default.
- W2056006593 hasConcept C178790620 @default.
- W2056006593 hasConcept C181199279 @default.