2014
Structure‐Based Evaluation of C5 Derivatives in the Catechol Diether Series Targeting HIV‐1 Reverse Transcriptase
Frey KM, Gray WT, Spasov KA, Bollini M, Gallardo‐Macias R, Jorgensen WL, Anderson KS. Structure‐Based Evaluation of C5 Derivatives in the Catechol Diether Series Targeting HIV‐1 Reverse Transcriptase. Chemical Biology & Drug Design 2014, 83: 541-549. PMID: 24289305, PMCID: PMC3999282, DOI: 10.1111/cbdd.12266.Peer-Reviewed Original ResearchConceptsHalogen-bonding interactionsCrystal structureHydrogen bondsAdditional hydrogen bond interactionC5 substitutionVan der Waals interactionsHydrogen-bonding interactionsAdditional crystal structuresDer Waals interactionsMore hydrogen bondsEffect of substituentsWaals interactionsClass of inhibitorsBackbone carbonylC5 substituentC5 positionComputational studyComparative structural analysisCatechol diethersStructure-based evaluationDerivativesSubstituentsHIV-1 reverse transcriptasePicomolar potencyBonds
2012
Crystal Structures of HIV‑1 Reverse Transcriptase with Picomolar Inhibitors Reveal Key Interactions for Drug Design
Frey KM, Bollini M, Mislak AC, Cisneros J, Gallardo-Macias R, Jorgensen WL, Anderson KS. Crystal Structures of HIV‑1 Reverse Transcriptase with Picomolar Inhibitors Reveal Key Interactions for Drug Design. Journal Of The American Chemical Society 2012, 134: 19501-19503. PMID: 23163887, PMCID: PMC3518392, DOI: 10.1021/ja3092642.Peer-Reviewed Original ResearchVirtual Screening and Optimization Yield Low-Nanomolar Inhibitors of the Tautomerase Activity of Plasmodium falciparum Macrophage Migration Inhibitory Factor
Dahlgren MK, Garcia AB, Hare AA, Tirado-Rives J, Leng L, Bucala R, Jorgensen WL. Virtual Screening and Optimization Yield Low-Nanomolar Inhibitors of the Tautomerase Activity of Plasmodium falciparum Macrophage Migration Inhibitory Factor. Journal Of Medicinal Chemistry 2012, 55: 10148-10159. PMID: 23067344, PMCID: PMC3509768, DOI: 10.1021/jm301269s.Peer-Reviewed Original ResearchConceptsImmune responsePlasmodium falciparum macrophage migration inhibitory factorInhibitory factorMacrophage migration inhibitory factorTautomerase activityMacrophage migratory inhibitory factorMigration inhibitory factorHost immune responseMalaria infectionSmall molecule inhibitorsCytokine activityHuman MIFHuman cytokinesPlasmodium falciparum orthologuePfMIFInhibitorsLow nanomolar inhibitorsScreeningVirtual screeningCytokinesEnzymatic siteActivityInfection
2007
Why Urea Eliminates Ammonia Rather than Hydrolyzes in Aqueous Solution
Alexandrova AN, Jorgensen WL. Why Urea Eliminates Ammonia Rather than Hydrolyzes in Aqueous Solution. The Journal Of Physical Chemistry B 2007, 111: 720-730. PMID: 17249815, PMCID: PMC2995377, DOI: 10.1021/jp066478s.Peer-Reviewed Original ResearchConceptsAddition/elimination mechanismDecomposition of ureaWater moleculesResonance stabilizationAqueous solutionNH3 eliminationNatural bond order analysisQM/MM Monte Carlo simulationsBond order analysisFree energy perturbation calculationsQM/MMExplicit water modelRate-determining stepElimination mechanismOverall free energyLow activation energySolvent effectsElimination reactionHydrogen bondsPreferred reaction routeReaction routeGas phaseTransition stateZwitterionic intermediateAb initio