AQUA-DUCT: a ligands tracking tool

Magdziarz, Tomasz; Mitusińska, Karolina; Goldowska, Sandra; Płuciennik, Alicja; Stolarczyk, Michał; Ługowska, Magdalena; Góra, Artur

doi:10.1093/bioinformatics/btx125

Cited by 26 publications

(22 citation statements)

References 8 publications

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“…Therefore, we decided to use water molecules as a kind of non-specific probe and performed detailed computational simulations to investigate possible mechanisms regulating solvent access to the active site to identify changes introduced by specific mutations. Molecular Dynamics simulations (MD) of DAAOs in water were done using AMBER package [ 48 ], the tunnel network analysis was performed using CAVER [ 49 ], and a water tracking study was done using AQUA-DUCT software [ 50 ]. The mentioned procedure was applied for pkDAAO, hDAAO and selected hDAAO mutants.…”

Section: Resultsmentioning

confidence: 99%

Modulating D-amino acid oxidase (DAAO) substrate specificity through facilitated solvent access

et al. 2018

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D-amino acid oxidase (DAAO) degrades D-amino acids to produce α-ketoacids, hydrogen peroxide and ammonia. DAAO has often been investigated and engineered for industrial and clinical applications. We combined information from literature with a detailed analysis of the structure to engineer mammalian DAAOs. The structural analysis was complemented with molecular dynamics simulations to characterize solvent accessibility and product release mechanisms. We identified non-obvious residues located on the loops on the border between the active site and the secondary binding pocket essential for pig and human DAAO substrate specificity and activity. We engineered DAAOs by mutating such critical residues and characterised the biochemical activity of the resulting variants. The results highlight the importance of the selected residues in modulating substrate specificity, product egress and enzyme activity, suggesting further steps of DAAO re-engineering towards desired clinical and industrial applications.

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Section: Resultsmentioning

confidence: 99%

Modulating D-amino acid oxidase (DAAO) substrate specificity through facilitated solvent access

et al. 2018

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“…Their tool consists of a set of linked views, enabling the exploration and filtering of trajectories, based on user‐defined criteria and thresholds. It integrates the clustering of trajectories, proposed by Góra et al [MMG*17]. However, our case studies revealed that experts sometimes need to investigate small‐scale interations between a single water molecule and a ligand in more detail.…”

Section: Related Workmentioning

confidence: 97%

Analysis of Long Molecular Dynamics Simulations Using Interactive Focus+Context Visualization

Trautner

Marques

Damborský

et al. 2019

Computer Graphics Forum

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Analyzing molecular dynamics (MD) simulations is a key aspect to understand protein dynamics and function. With increasing computational power, it is now possible to generate very long and complex simulations, which are cumbersome to explore using traditional 3D animations of protein movements. Guided by requirements derived from multiple focus groups with protein engineering experts, we designed and developed a novel interactive visual analysis approach for long and crowded MD simulations. In this approach, we link a dynamic 3D focus+context visualization with a 2D chart of time series data to guide the detection and navigation towards important spatio‐temporal events. The 3D visualization renders elements of interest in more detail and increases the temporal resolution dependent on the time series data or the spatial region of interest. In case studies with different MD simulation data sets and research questions, we found that the proposed visual analysis approach facilitates exploratory analysis to generate, confirm, or reject hypotheses about causalities. Finally, we derived design guidelines for interactive visual analysis of complex MD simulation data.

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“…AQUA-DUCT [62,63] aims to provide detailed insights into the process of how a given type of molecules, such as water, ions, gasses, or any other kind of ligand, penetrates through the selected region of a protein ( Figure 3A). As a minimal input, the user has to provide an MD trajectory and a configuration file describing two important regions for the analysis and defining the traced ligand.…”

Section: Analyses Of Ligand Transportmentioning

confidence: 99%

“…Additionally, a statistical analysis is performed for all clusters, enumerating the number of the evaluated molecules, paths, inlets, and clusters, and several more specific statistics, including the lengths of the paths or the durations of the transport events. To illustrate the computational demands, the AQUA-DUCT analysis of 100 ns long MD simulations of murine epoxide hydrolase (4992 protein atoms) surrounded by 8488 water molecules requires 8-12 h to execute on a powerful workstation (Intel Core i7 CPU @ 3.50GHz machine, 64 GB RAM) [62]. For visualization purposes, a PyMOL [82] script or session can be generated according to user specifications.…”

Section: Analyses Of Ligand Transportmentioning

confidence: 99%

Dynamics, a Powerful Component of Current and Future in Silico Approaches for Protein Design and Engineering

Surpeta

Sequeiros-Borja

Brezovský

2020

IJMS

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Computational prediction has become an indispensable aid in the processes of engineering and designing proteins for various biotechnological applications. With the tremendous progress in more powerful computer hardware and more efficient algorithms, some of in silico tools and methods have started to apply the more realistic description of proteins as their conformational ensembles, making protein dynamics an integral part of their prediction workflows. To help protein engineers to harness benefits of considering dynamics in their designs, we surveyed new tools developed for analyses of conformational ensembles in order to select engineering hotspots and design mutations. Next, we discussed the collective evolution towards more flexible protein design methods, including ensemble-based approaches, knowledge-assisted methods, and provable algorithms. Finally, we highlighted apparent challenges that current approaches are facing and provided our perspectives on their further development.

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AQUA-DUCT: a ligands tracking tool

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 26 publications

References 8 publications

Modulating D-amino acid oxidase (DAAO) substrate specificity through facilitated solvent access

Modulating D-amino acid oxidase (DAAO) substrate specificity through facilitated solvent access

Analysis of Long Molecular Dynamics Simulations Using Interactive Focus+Context Visualization

Dynamics, a Powerful Component of Current and Future in Silico Approaches for Protein Design and Engineering

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