The ModFOLD4 server for the quality assessment of 3D protein models

McGuffin, Liam J.; Buenavista, Maria T.; Roche, Daniel B.

doi:10.1093/nar/gkt294

Cited by 105 publications

(83 citation statements)

References 26 publications

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“…The TBEV structure was modeled using Modeler (34). The models were evaluated using the protein model-qualifying servers ModFOLD, QMEAN, and RESPROX (35)(36)(37). Based on a consensus, the best-ranked TBEV model was then selected for subsequent in silico experiments.…”

Section: Methodsmentioning

confidence: 99%

Nucleoside Inhibitors of Tick-Borne Encephalitis Virus

Eyer

Valdés

Gil

et al. 2015

Antimicrob Agents Chemother

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The anti-TBEV effect of 2=-CMA in cell culture diminished gradually after day 3 posttreatment. 7-Deaza-2=-CMA showed no detectable cellular toxicity (CC 50 > 50 M), and the antiviral effect in culture was stable for >6 days posttreatment. Computational molecular analyses revealed that compared to the other two compounds, 7-deaza-2=-CMA formed a large cluster near the active site of the TBEV polymerase. High antiviral activity and low cytotoxicity suggest that 7-deaza-2=-CMA is a promising candidate for further investigation as a potential therapeutic agent in treating TBEV infection.

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Section: Methodsmentioning

confidence: 99%

Nucleoside Inhibitors of Tick-Borne Encephalitis Virus

Eyer

Valdés

Gil

et al. 2015

Antimicrob Agents Chemother

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“…We report that computational MANUSCRIPT 5 analysis approximating flavonoid interactions with modelled and crystallised kinases, together with biological validation, may direct and accelerate virtual screening studies for translation of these compounds into selective and potent small-molecule inhibitors applied to the discovery of therapeutic agents for vascular disorders. ModFOLD server (http://www.reading.ac.uk/bioinf/ModFOLD/) [38][39] was used to evaluate global and local model quality prior to docking.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The per-residue error was predicted using the ModFOLD server [38,[62][63]. The colour-coding used by ModFOLD represents the residue accuracy according to a pseudo-temperature scheme (blue indicates residues closest to the native structure; red, those furthest from the native structure).…”

Section: Homology Modellingmentioning

confidence: 99%

GRID and docking analyses reveal a molecular basis for flavonoid inhibition of Src family kinase activity

Wright¹,

Watson²,

McGuffin³

et al. 2015

The Journal of Nutritional Biochemistry

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Flavonoids reduce cardiovascular disease risk through anti-inflammatory, anti-coagulant and anti-platelet actions. One key flavonoid inhibitory mechanism is blocking kinase activity that drives these processes. Flavonoids attenuate activities of kinases including phosphoinositide-3-kinase, Fyn, Lyn, Src, Syk, PKC, PIM1/2, ERK, JNK and PKA. X-ray crystallographic analyses of kinase-flavonoid complexes show that flavonoid ring systems and their hydroxyl substitutions are important structural features for their binding to kinases. A clearer understanding of structural interactions of flavonoids with kinases is necessary to allow construction of more potent and selective counterparts. We examined flavonoid (quercetin, apigenin and catechin) interactions with Src family kinases (Lyn, Fyn and Hck) applying the Sybyl docking algorithm and GRID. A homology model (Lyn) was used in our analyses to demonstrate that high-quality predicted kinase structures are suitable for flavonoid computational studies. Our docking results revealed potential hydrogen bond contacts between flavonoid hydroxyls and kinase catalytic site residues. Identification of plausible contacts indicated that quercetin formed the most energetically stable interactions, apigenin lacked hydroxyl groups necessary for important contacts and the non-planar structure of catechin could not support predicted hydrogen bonding patterns. GRID analysis using a hydroxyl functional group supported docking results. Based on these findings, we predicted that quercetin would inhibit activities of Src family kinases with greater potency than apigenin and catechin. We validated this prediction using in vitro kinase assays. We conclude that our study can be used as a basis to construct virtual flavonoid interaction libraries to guide drug discovery using these compounds as molecular templates.

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“…Models were based on the template 3s57 chain a of the human aBH2 protein and were built and evaluated using the intFOLD, i-tassEr and ModFOLD4 servers and the sParKs-x and Modeler standalone programs. [73][74][75][76] Details of the modeling approach are provided in the Supplementary Material. the images of models were rendered using PyMOL.…”

Section: Expression and Tissue Distribution Of Dtet And Dnmt2mentioning

confidence: 99%