Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• -dimensional structure of a disease-related drug target is known, the most commonly used CADD techniques are structure-based. In SBDD the therapeutics are designed based on the knowledge of the target structure. Two commonly used methods in SBDD are molecular docking approaches and de novo ligand (antagonists

• ) protease is a prime drug target for anti-AIDS therapeutics. In the early 1990s many approved HIV protease inhibitors were developed to target HIV infections using structure-based molecular docking. It was a ground breaking success at that time and made it possible for HIV infected individuals to live

• docking In molecular docking, how well a drug binds to its target is determined by the binding affinity prediction of the pose. This is done by scoring. Scoring is used to evaluate and rank the target–ligand complexes predicted by docking algorithms. Scoring functions are used in SBDD for scoring and

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• -containing derivatives are biologically interesting (Figure 1) [7]. In addition, molecular docking studies have been performed and highlighted the importance of three binding areas within the active site of the protein: a hydrophobic clamp (Phe157, His209 and Tyr210) interacting with the nucleobase, a

• which they block the enzyme activity. For this purpose, a SAR study was carried out by molecular docking. Attempts to make a direct correlation between the inhibitory activity and the gold-computed docking score (Table 2) were unsuccessful. Indeed, all compounds exhibited a similar score with a value

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• order to further explore the possibility that compound 4 may act as a LasR antagonist, it was subjected to molecular docking studies against the P. aeruginosa LasR ligand–binding domain (LBD) [31]. Specifically, both OdDHL and 4 were docked into the OdDHL binding pocket of two LasR LBD structures, one

Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?

• Tobias-Elias Gloe,
• Insa Stamer,
• Cornelia Hojnik,
• Tanja M. Wrodnigg and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 1096–1104, doi:10.3762/bjoc.11.123

• E. coli bacteria by means of molecular docking and bacterial adhesion studies. It turns out that Amadori rearrangement products have a limited activity as inhibitors of bacterial adhesion because the β-C-glycosidically linked aglycone considerably hampers complexation within the carbohydrate binding

• predictions made by molecular docking, inhibition–adhesion studies using type 1-fimbriated fluorescent E. coli were performed [30]. Accordingly, the manno-configured glycosides 9 and 10 were used as inhibitors of FimH-mediated bacterial adhesion to mannan employing a microtiter plate format and GFP

• group at the anomeric centre. Molecular docking of both Amadori products, 9 and 10, into FimH suggested a reasonable binding mode, however in biological testing 9 and 10 showed an approx. 0.4 and 0.2 fold weaker potency as inhibitors of FimH-mediated bacterial adhesion than MeMan (1). This can be

Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes

• Bodee Nutho,
• Wasinee Khuntawee,
• Chompoonut Rungnim,
• Piamsook Pongsawasdi,
• Peter Wolschann,
• Alfred Karpfen,
• Nawee Kungwan and
• Thanyada Rungrotmongkol

Beilstein J. Org. Chem. 2014, 10, 2789–2799, doi:10.3762/bjoc.10.296

• to investigate the preferential binding mode and encapsulation of the flavonoid fisetin in the nano-pore of β-cyclodextrin (β-CD) at the molecular level using various theoretical approaches: molecular docking, molecular dynamics (MD) simulations and binding free energy calculations. The molecular

• understand the two flavonoids/β-CD complexes, hesperetin and naringenin complexes, in aqueous solution. The PM3 method was applied to calculate the energy regarding the antioxidant property of the flavonoid chysin in the complex with β-CD [32]. Interestingly, the molecular docking study on the fisetin/β-CD

• (48.8%) and III (21.1%). By considering the percentage of occurrence, it can be implied that complexation with β-CD was preferentially formed through the phenyl ring of fisetin. However, molecular docking in the gas phase may be insufficient for the determination of the structure and the stability of

Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• predict potential targets of the newly synthesized library of β-carboline-containing compounds. High-throughput docking studies for protein-target prediction of newly synthesized compounds Molecular docking studies were performed with the 34 newly synthesized compounds, represented by scaffolds 1, 2, 3

Dipyridodiazepinone derivatives; synthesis and anti HIV-1 activity

• Nisachon Khunnawutmanotham,
• Nitirat Chimnoi,
• Arunee Thitithanyanont,
• Patchreenart Saparpakorn,
• Kiattawee Choowongkomon,
• Pornpan Pungpo,
• Supa Hannongbua and
• Supanna Techasakul

Beilstein J. Org. Chem. 2009, 5, No. 36, doi:10.3762/bjoc.5.36

• groups in 7 and 8 led to diminished activity relative to that of 5 and 6. 10 and 11, 8-amino analogues of nevirapine, were found to be ineffective inhibitors. Molecular docking To understand the binding mode of the new potent derivatives 5, 6 and 9 were docked into the HIV-1 RT binding site by using the