Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308635391> ?p ?o ?g. }
- W4308635391 endingPage "5549" @default.
- W4308635391 startingPage "5536" @default.
- W4308635391 abstract "Drug-target residence time has emerged as a key selection factor in drug discovery since the binding duration of a drug molecule to its protein target can significantly impact its in vivo efficacy. The challenge in studying the residence time, in early drug discovery stages, lies in how to cost-effectively determine the residence time for the systematic assessment of compounds. Currently, there is still a lack of computational protocols to quickly estimate such a measure, particularly for large and flexible protein targets and drugs. Here, we report an efficient computational protocol, based on targeted molecular dynamics, to rank drug candidates by their residence time and to obtain insights into ligand–target dissociation mechanisms. The method was assessed on a dataset of 10 arylpyrazole inhibitors of CDK8, a large, flexible, and clinically important target, for which the experimental residence time of the inhibitors ranges from minutes to hours. The compounds were correctly ranked according to their estimated residence time scores compared to their experimental values. The analysis of protein–ligand interactions along the dissociation trajectories highlighted the favorable contribution of hydrophobic contacts to residence time and revealed key residues that strongly affect compound residence time." @default.
- W4308635391 created "2022-11-13" @default.
- W4308635391 creator A5003235955 @default.
- W4308635391 creator A5027241504 @default.
- W4308635391 creator A5037970680 @default.
- W4308635391 creator A5039346535 @default.
- W4308635391 creator A5057496649 @default.
- W4308635391 creator A5090027634 @default.
- W4308635391 date "2022-11-09" @default.
- W4308635391 modified "2023-09-30" @default.
- W4308635391 title "Estimation of Drug-Target Residence Time by Targeted Molecular Dynamics Simulations" @default.
- W4308635391 cites W1230652463 @default.
- W4308635391 cites W1587498640 @default.
- W4308635391 cites W1829424643 @default.
- W4308635391 cites W1959100396 @default.
- W4308635391 cites W1968571642 @default.
- W4308635391 cites W1968779484 @default.
- W4308635391 cites W1969723894 @default.
- W4308635391 cites W1984658396 @default.
- W4308635391 cites W1986191025 @default.
- W4308635391 cites W1992192767 @default.
- W4308635391 cites W2001357862 @default.
- W4308635391 cites W2006932016 @default.
- W4308635391 cites W2012529917 @default.
- W4308635391 cites W2015688756 @default.
- W4308635391 cites W2023152464 @default.
- W4308635391 cites W2029667189 @default.
- W4308635391 cites W2037535298 @default.
- W4308635391 cites W2048350769 @default.
- W4308635391 cites W2063945425 @default.
- W4308635391 cites W2065283382 @default.
- W4308635391 cites W2123967889 @default.
- W4308635391 cites W2125446149 @default.
- W4308635391 cites W2127322768 @default.
- W4308635391 cites W2128307445 @default.
- W4308635391 cites W2133620840 @default.
- W4308635391 cites W2134994679 @default.
- W4308635391 cites W2147491346 @default.
- W4308635391 cites W2147993766 @default.
- W4308635391 cites W2158730443 @default.
- W4308635391 cites W2265661434 @default.
- W4308635391 cites W2281340876 @default.
- W4308635391 cites W2312634253 @default.
- W4308635391 cites W2313946970 @default.
- W4308635391 cites W2327787157 @default.
- W4308635391 cites W2330799739 @default.
- W4308635391 cites W2335543360 @default.
- W4308635391 cites W2346590986 @default.
- W4308635391 cites W2404280981 @default.
- W4308635391 cites W2413651855 @default.
- W4308635391 cites W2414725821 @default.
- W4308635391 cites W2461189873 @default.
- W4308635391 cites W2464012090 @default.
- W4308635391 cites W2575009204 @default.
- W4308635391 cites W2581729559 @default.
- W4308635391 cites W2588867992 @default.
- W4308635391 cites W2593262867 @default.
- W4308635391 cites W2598374175 @default.
- W4308635391 cites W2607348308 @default.
- W4308635391 cites W2616655501 @default.
- W4308635391 cites W2620254666 @default.
- W4308635391 cites W2621922190 @default.
- W4308635391 cites W2735354780 @default.
- W4308635391 cites W2741577472 @default.
- W4308635391 cites W2756965977 @default.
- W4308635391 cites W2767492466 @default.
- W4308635391 cites W2769077630 @default.
- W4308635391 cites W2776596084 @default.
- W4308635391 cites W2801926893 @default.
- W4308635391 cites W2804603144 @default.
- W4308635391 cites W2952082641 @default.
- W4308635391 cites W2972051445 @default.
- W4308635391 cites W3004735288 @default.
- W4308635391 cites W3008279928 @default.
- W4308635391 cites W3121332380 @default.
- W4308635391 cites W3125480257 @default.
- W4308635391 cites W3159738363 @default.
- W4308635391 cites W3167895336 @default.
- W4308635391 cites W4285744851 @default.
- W4308635391 doi "https://doi.org/10.1021/acs.jcim.2c00852" @default.
- W4308635391 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36350238" @default.
- W4308635391 hasPublicationYear "2022" @default.
- W4308635391 type Work @default.
- W4308635391 citedByCount "2" @default.
- W4308635391 countsByYear W43086353912023 @default.
- W4308635391 crossrefType "journal-article" @default.
- W4308635391 hasAuthorship W4308635391A5003235955 @default.
- W4308635391 hasAuthorship W4308635391A5027241504 @default.
- W4308635391 hasAuthorship W4308635391A5037970680 @default.
- W4308635391 hasAuthorship W4308635391A5039346535 @default.
- W4308635391 hasAuthorship W4308635391A5057496649 @default.
- W4308635391 hasAuthorship W4308635391A5090027634 @default.
- W4308635391 hasConcept C127413603 @default.
- W4308635391 hasConcept C144024400 @default.
- W4308635391 hasConcept C147597530 @default.
- W4308635391 hasConcept C149923435 @default.
- W4308635391 hasConcept C185592680 @default.
- W4308635391 hasConcept C187320778 @default.