ballaxy: web services for structural bioinformatics

Hildebrandt, Andreas; Stöckel, Daniel; Fischer, Nina; Garza, Luis de la; Krüger, Jens; Nickels, Stefan; Röttig, Marc; Schärfe, Charlotta; Schumann, Marcel; Thiel, Philipp; Lenhof, Hans‐Peter; Kohlbacher, Oliver; Hildebrandt, Andreas

doi:10.1093/bioinformatics/btu574

Cited by 11 publications

(5 citation statements)

References 9 publications

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“…Rescoring of the docked poses using was carried out using pairwise linear potential (PLP), Poisson–Boltzmann (PB), and molecular mechanics (MM) scoring functions − in the Galaxy/Ballaxy software. A Spearman’s rank value based on the consensus score for each of the MAT isoforms and the experimental activity of the NPS was then calculated.…”

Section: Methodsmentioning

confidence: 99%

In Silico Investigations into the Selectivity of Psychoactive and New Psychoactive Substances in Monoamine Transporters

Botha

Kirton

2022

ACS Omega

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New psychoactive substances (NPS) are a group of compounds that mimic the effects of illicit substances. A range of NPS have been shown to interact with the three main classes of monoamine transporters (DAT, NET, and SERT) to differing extents, but it is unclear why these differences arise. To aid in understanding the differences in affinity between the classes of monoamine transporters, several in silico experiments were conducted. Docking experiments showed there was no direct correlation between a range of scoring functions and experimental activity, but Spearman ranking analysis showed a significant correlation (α = 0.1) for DAT, with the affinity ΔG (0.42), αHB (0.40), GoldScore (0.40), and PLP (0.41) scoring functions, and for DAT (0.38) and SERT (0.40) using a consensus scoring approach. Qualitative structure–activity relationship (QSAR) experiments resulted in the generation of robust and predictive three-descriptor models for SERT (r 2 = 0.87, q 2 = 0.8, and test set r 2 = 0.74) and DAT (r 2 = 0.68, q 2 = 0.51, test set r 2 = 0.63). Both QSAR models described similar characteristics for binding, i.e., rigid hydrophobic molecules with a biogenic amine moiety, and were not sufficient to facilitate a deeper understanding of differences in affinity between the monoamine transporters. This contextualizes the observed promiscuity for NPS between the isoforms and highlights the difficulty in the design and development of compounds that are isoform-selective.

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Section: Methodsmentioning

confidence: 99%

In Silico Investigations into the Selectivity of Psychoactive and New Psychoactive Substances in Monoamine Transporters

Botha

Kirton

2022

ACS Omega

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“…Fifty poses were retained for each docking, and duplicate poses were removed from the analysis. The online server Ballaxy [ 38 ] was used to rescore high-ranked poses in an effort to eliminate scoring function bias. Any poses not re-scored highly were removed from further analysis.…”

Section: Methodsmentioning

confidence: 99%

Discovery of novel small molecule inhibitors of S100P with in vitro anti-metastatic effects on pancreatic cancer cells

Camara

Ogbeni

Gerstmann

et al. 2020

European Journal of Medicinal Chemistry

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S100P, a calcium-binding protein, is known to advance tumor progression and metastasis in pancreatic and several other cancers. Herein is described the in silico identification of a putative binding pocket of S100P to identify, synthesize and evaluate novel small molecules with the potential to selectively bind S100P and inhibit its activation of cell survival and metastatic pathways. The virtual screening of a drug-like database against the S100P model led to the identification of over 100 clusters of diverse scaffolds. A representative test set identified a number of structurally unrelated hits that inhibit S100P-RAGE interaction, measured by ELISA, and reduce in vitro cell invasion selectively in S100P-expressing pancreatic cancer cells at 10 μM. This study establishes a proof of concept in the potential for rational design of small molecule S100P inhibitors for drug candidate development.

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“…As a third option, BALL comes with a versatile command line tool for clustering that can be used in a stand-alone fashion or integrated into larger shell scripts. Finally, we provide bindings for our ballaxy-server (Hildebrandt et al, 2015), an adaptation of the popular web-based Galaxy workflow system to structural biology applications (see Figure 2).…”

Section: Integration Into the Biochemical Algorithms Librarymentioning

confidence: 99%

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2017

The International Journal of High Performance Computing Applica

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Clustering of molecular systems according to their three-dimensional structure is an important step in many bioinformatics workflows. In applications such as docking or structure prediction, many algorithms initially generate large numbers of candidate poses (or decoys), which are then clustered to allow for subsequent computationally expensive evaluations of reasonable representatives. Since the number of such candidates can easily range from thousands to millions, performing the clustering on standard central processing units (CPUs) is highly time consuming. In this paper, we analyse and evaluate different approaches to parallelize the nearest neighbour chain algorithm to perform hierarchical Ward clustering of protein structures, using both atom-based root mean square deviation (RMSD) and rigid-body RMSD molecular distances on a graphics processing unit (GPU). This leads to a speedup of around one order of magnitude of our CUDA implementation on a GeForce Titan GPU compared to a multi-threaded CPU implementation on a Core-i7 2700. Furthermore, the runtimes compare favourably with ClusCo, another state-of-the-art CUDA-enabled protein structure clustering method, while achieving similar accuracy on the iTasser benchmark dataset. Our implementation has also been incorporated into the Biochemical Algorithms library to allow easy integration into biologists' workflows.

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ballaxy: web services for structural bioinformatics

Cited by 11 publications

References 9 publications

In Silico Investigations into the Selectivity of Psychoactive and New Psychoactive Substances in Monoamine Transporters

In Silico Investigations into the Selectivity of Psychoactive and New Psychoactive Substances in Monoamine Transporters

Discovery of novel small molecule inhibitors of S100P with in vitro anti-metastatic effects on pancreatic cancer cells

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