FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4296050548> ?p ?o ?g. }

• W4296050548 endingPage "101093" @default.
• W4296050548 startingPage "101093" @default.
• W4296050548 abstract "The effort to eradicate malaria has not yet been achieved, and the parasitic infection remains a global challenge. The burden stems from the worldwide dissemination of parasites resistant to commonly used chemotherapeutics and the scarcity of the malaria vaccine, Mosquirix. In the quest to augment malaria treatment, current focus has been geared towards plasmepsin (P). These classes of aspartic acid proteases are expressed at multiple stages of the parasite's life cycle and are implicated in host haemoglobin degradation and parasite dissemination in vivo; elaborating their essentiality as therapeutic targets. Our earlier research examined the structural dynamics of WM382, a novel antimalarial compound, in relation to its enzyme inhibitory mechanism on plasmepsin IX (PMIX) and plasmepsin X (PMX). WM382 inflicts structural compactness on both proteases. The pharmacophoric moieties of WM382 were used in the present study to search the Zinc database for WM382 derivatives. The leads, ZINC06868602, ZINC09431717 and ZINC13367223 formed strong intermolecular bonds with the catalytic dyad Asp32 and Asp281. The flap regions generally move away from the binding pocket, divulging the active site to the inhibitor and keeping it near to the catalytic dyad. However, upon binding of the leads, the flap residues wrapped inward to surround the inhibitors further restricting the characteristic twist motion of these proteases for enzyme activity. Likewise, the experimental drug candidate WM382, the identified leads displayed high affinity for PMIX, with total binding free energies of leads estimated to be −33.45 kcal/mol, −30.33 kcal/mol and −29.67 kcal/mol, respectively. Evaluation of per residue energy composition indicated the catalytic dyad contributes immensely towards ligand binding. Results from our study suggest these compounds have better inhibitory prowess against PMIX. The potency of these chemicals should further be tested in the experimental laboratory to evaluate their usefulness." @default.
• W4296050548 created "2022-09-17" @default.
• W4296050548 creator A5021219358 @default.
• W4296050548 creator A5030380866 @default.
• W4296050548 creator A5070955314 @default.
• W4296050548 creator A5078673820 @default.
• W4296050548 creator A5082770429 @default.
• W4296050548 date "2022-01-01" @default.
• W4296050548 modified "2023-09-25" @default.
• W4296050548 title "Disrupting the characteristic twist motion; tailored in silico approach towards the design of plasmepsin inhibitors" @default.
• W4296050548 cites W1552369200 @default.
• W4296050548 cites W1991741354 @default.
• W4296050548 cites W2051815026 @default.
• W4296050548 cites W2060809301 @default.
• W4296050548 cites W2075369230 @default.
• W4296050548 cites W2104439228 @default.
• W4296050548 cites W2162853638 @default.
• W4296050548 cites W2165174924 @default.
• W4296050548 cites W2168918061 @default.
• W4296050548 cites W2742753960 @default.
• W4296050548 cites W2784798198 @default.
• W4296050548 cites W2897041437 @default.
• W4296050548 cites W2901677424 @default.
• W4296050548 cites W2976202521 @default.
• W4296050548 cites W2977776930 @default.
• W4296050548 cites W3008996229 @default.
• W4296050548 cites W3021798720 @default.
• W4296050548 cites W3022591587 @default.
• W4296050548 cites W3121915585 @default.
• W4296050548 doi "https://doi.org/10.1016/j.imu.2022.101093" @default.
• W4296050548 hasPublicationYear "2022" @default.
• W4296050548 type Work @default.
• W4296050548 citedByCount "0" @default.
• W4296050548 crossrefType "journal-article" @default.
• W4296050548 hasAuthorship W4296050548A5021219358 @default.
• W4296050548 hasAuthorship W4296050548A5030380866 @default.
• W4296050548 hasAuthorship W4296050548A5070955314 @default.
• W4296050548 hasAuthorship W4296050548A5078673820 @default.
• W4296050548 hasAuthorship W4296050548A5082770429 @default.
• W4296050548 hasBestOaLocation W42960505481 @default.
• W4296050548 hasConcept C104317684 @default.
• W4296050548 hasConcept C107824862 @default.
• W4296050548 hasConcept C181199279 @default.
• W4296050548 hasConcept C182220744 @default.
• W4296050548 hasConcept C185592680 @default.
• W4296050548 hasConcept C2524010 @default.
• W4296050548 hasConcept C2775905019 @default.
• W4296050548 hasConcept C2776196297 @default.
• W4296050548 hasConcept C33923547 @default.
• W4296050548 hasConcept C41183919 @default.
• W4296050548 hasConcept C55493867 @default.
• W4296050548 hasConcept C70721500 @default.
• W4296050548 hasConcept C71240020 @default.
• W4296050548 hasConcept C74187038 @default.
• W4296050548 hasConcept C86803240 @default.
• W4296050548 hasConceptScore W4296050548C104317684 @default.
• W4296050548 hasConceptScore W4296050548C107824862 @default.
• W4296050548 hasConceptScore W4296050548C181199279 @default.
• W4296050548 hasConceptScore W4296050548C182220744 @default.
• W4296050548 hasConceptScore W4296050548C185592680 @default.
• W4296050548 hasConceptScore W4296050548C2524010 @default.
• W4296050548 hasConceptScore W4296050548C2775905019 @default.
• W4296050548 hasConceptScore W4296050548C2776196297 @default.
• W4296050548 hasConceptScore W4296050548C33923547 @default.
• W4296050548 hasConceptScore W4296050548C41183919 @default.
• W4296050548 hasConceptScore W4296050548C55493867 @default.
• W4296050548 hasConceptScore W4296050548C70721500 @default.
• W4296050548 hasConceptScore W4296050548C71240020 @default.
• W4296050548 hasConceptScore W4296050548C74187038 @default.
• W4296050548 hasConceptScore W4296050548C86803240 @default.
• W4296050548 hasFunder F4320322812 @default.
• W4296050548 hasLocation W42960505481 @default.
• W4296050548 hasLocation W42960505482 @default.
• W4296050548 hasOpenAccess W4296050548 @default.
• W4296050548 hasPrimaryLocation W42960505481 @default.
• W4296050548 hasRelatedWork W116031781 @default.
• W4296050548 hasRelatedWork W2003194288 @default.
• W4296050548 hasRelatedWork W2006002595 @default.
• W4296050548 hasRelatedWork W2054118966 @default.
• W4296050548 hasRelatedWork W2092236356 @default.
• W4296050548 hasRelatedWork W2146211839 @default.
• W4296050548 hasRelatedWork W2181705536 @default.
• W4296050548 hasRelatedWork W2491451478 @default.
• W4296050548 hasRelatedWork W2605628782 @default.
• W4296050548 hasRelatedWork W4386100014 @default.
• W4296050548 hasVolume "33" @default.
• W4296050548 isParatext "false" @default.
• W4296050548 isRetracted "false" @default.
• W4296050548 workType "article" @default.