Matches in SemOpenAlex for { <https://semopenalex.org/work/W2892790483> ?p ?o ?g. }
- W2892790483 endingPage "6107" @default.
- W2892790483 startingPage "6099" @default.
- W2892790483 abstract "Intrinsically disordered proteins play vital roles in biology, and their dysfunction contributes to many major disease states. These proteins remain challenging targets for rational ligand discovery or drug design because they are highly dynamic and fluctuate through a diverse set of conformations, frustrating structure-based approaches. To meet this challenge, we have developed protocols to efficiently identify active small molecule ligands of disordered proteins. Our approach utilizes enhanced sampling molecular dynamics and conformational analysis approaches optimized for disordered targets, coupled with computational docking and machine learning-based screens of compound libraries. By applying this protocol to an amyloid-forming segment of microtubule-associated protein tau, we successfully identified novel, chemically diverse tau ligands, including an inhibitor that delays the aggregation reaction in vitro without affecting the amount of aggregate formed at the steady state. Our results indicate that we have expanded the toolkit of protein aggregation inhibitors into new areas of chemical space and demonstrate the feasibility of our ligand discovery strategy." @default.
- W2892790483 created "2018-10-05" @default.
- W2892790483 creator A5025676009 @default.
- W2892790483 creator A5043831643 @default.
- W2892790483 date "2018-09-24" @default.
- W2892790483 modified "2023-09-24" @default.
- W2892790483 title "The Rational Discovery of a Tau Aggregation Inhibitor" @default.
- W2892790483 cites W155626891 @default.
- W2892790483 cites W1568323816 @default.
- W2892790483 cites W1571193377 @default.
- W2892790483 cites W1592633314 @default.
- W2892790483 cites W1965361199 @default.
- W2892790483 cites W1966078827 @default.
- W2892790483 cites W1966442040 @default.
- W2892790483 cites W1966521458 @default.
- W2892790483 cites W1970022221 @default.
- W2892790483 cites W1970577444 @default.
- W2892790483 cites W1971677273 @default.
- W2892790483 cites W1975121208 @default.
- W2892790483 cites W1976638865 @default.
- W2892790483 cites W1978338367 @default.
- W2892790483 cites W1985884834 @default.
- W2892790483 cites W1985921281 @default.
- W2892790483 cites W1997980735 @default.
- W2892790483 cites W2002900801 @default.
- W2892790483 cites W2004884414 @default.
- W2892790483 cites W2006322736 @default.
- W2892790483 cites W2009455776 @default.
- W2892790483 cites W2011149432 @default.
- W2892790483 cites W2022417585 @default.
- W2892790483 cites W2023156380 @default.
- W2892790483 cites W2025872362 @default.
- W2892790483 cites W2026050478 @default.
- W2892790483 cites W2032208441 @default.
- W2892790483 cites W2032363535 @default.
- W2892790483 cites W2034016778 @default.
- W2892790483 cites W2045873232 @default.
- W2892790483 cites W2047189301 @default.
- W2892790483 cites W2049291900 @default.
- W2892790483 cites W2051370550 @default.
- W2892790483 cites W205316367 @default.
- W2892790483 cites W2053758288 @default.
- W2892790483 cites W2057915818 @default.
- W2892790483 cites W2058233568 @default.
- W2892790483 cites W2064367582 @default.
- W2892790483 cites W2065833476 @default.
- W2892790483 cites W2084606558 @default.
- W2892790483 cites W2091752317 @default.
- W2892790483 cites W2095729147 @default.
- W2892790483 cites W2099991048 @default.
- W2892790483 cites W2102696255 @default.
- W2892790483 cites W2105029490 @default.
- W2892790483 cites W2108102848 @default.
- W2892790483 cites W2108191354 @default.
- W2892790483 cites W2113156999 @default.
- W2892790483 cites W2118608964 @default.
- W2892790483 cites W2125012012 @default.
- W2892790483 cites W2126099124 @default.
- W2892790483 cites W2127713467 @default.
- W2892790483 cites W2134967712 @default.
- W2892790483 cites W2142366168 @default.
- W2892790483 cites W2144925005 @default.
- W2892790483 cites W2145653859 @default.
- W2892790483 cites W2146833115 @default.
- W2892790483 cites W2165779834 @default.
- W2892790483 cites W2167279371 @default.
- W2892790483 cites W2169678694 @default.
- W2892790483 cites W2177317049 @default.
- W2892790483 cites W2237013109 @default.
- W2892790483 cites W2282251269 @default.
- W2892790483 cites W2301705357 @default.
- W2892790483 cites W2309048437 @default.
- W2892790483 cites W2326962045 @default.
- W2892790483 cites W2339559661 @default.
- W2892790483 cites W2469457850 @default.
- W2892790483 cites W2552763360 @default.
- W2892790483 cites W2554784405 @default.
- W2892790483 cites W2604427100 @default.
- W2892790483 cites W2690412492 @default.
- W2892790483 cites W2727929522 @default.
- W2892790483 cites W2743471889 @default.
- W2892790483 cites W2750503472 @default.
- W2892790483 cites W2769171126 @default.
- W2892790483 cites W2782157905 @default.
- W2892790483 cites W2784102787 @default.
- W2892790483 cites W4243199283 @default.
- W2892790483 cites W902862997 @default.
- W2892790483 doi "https://doi.org/10.1021/acs.biochem.8b00581" @default.
- W2892790483 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7021323" @default.
- W2892790483 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30247897" @default.
- W2892790483 hasPublicationYear "2018" @default.
- W2892790483 type Work @default.
- W2892790483 sameAs 2892790483 @default.
- W2892790483 citedByCount "20" @default.
- W2892790483 countsByYear W28927904832019 @default.
- W2892790483 countsByYear W28927904832020 @default.
- W2892790483 countsByYear W28927904832021 @default.
- W2892790483 countsByYear W28927904832022 @default.