• This record comes from PubMed

Interactive exploration of ligand transportation through protein tunnels

. 2017 Feb 15 ; 18 (Suppl 2) : 22. [epub] 20170215

Language English Country England, Great Britain Media electronic

Document type Journal Article

Links

PubMed 28251878
PubMed Central PMC5333178
DOI 10.1186/s12859-016-1448-0
PII: 10.1186/s12859-016-1448-0
Knihovny.cz E-resources

BACKGROUND: Protein structures and their interaction with ligands have been in the focus of biochemistry and structural biology research for decades. The transportation of ligand into the protein active site is often complex process, driven by geometric and physico-chemical properties, which renders the ligand path full of jitter and impasses. This prevents understanding of the ligand transportation and reasoning behind its behavior along the path. RESULTS: To address the needs of the domain experts we design an explorative visualization solution based on a multi-scale simplification model. It helps to navigate the user to the most interesting parts of the ligand trajectory by exploring different attributes of the ligand and its movement, such as its distance to the active site, changes of amino acids lining the ligand, or ligand "stuckness". The process is supported by three linked views - 3D representation of the simplified trajectory, scatterplot matrix, and bar charts with line representation of ligand-lining amino acids. CONCLUSIONS: The usage of our tool is demonstrated on molecular dynamics simulations provided by the domain experts. The tool was tested by the domain experts from protein engineering and the results confirm that it helps to navigate the user to the most interesting parts of the ligand trajectory and to understand the ligand behavior.

See more in PubMed

Koudelakova T, Chaloupkova R, Brezovsky J, Prokop Z, Sebestova E, Hesseler M, Khabiri M, Plevaka M, Kulik D, Kuta Smatanova I, Rezacova P, Ettrich R, Bornscheuer UT, Damborsky J. Engineering enzyme stability and resistance to an organic cosolvent by modification of residues in the access tunnel. Angew Chem Int Ed. 2013;52(7):1959–1963. doi: 10.1002/anie.201206708. PubMed DOI

Chovancova E, Pavelka A, Benes P, Strnad O, Brezovsky J, Kozlikova B, Gora A, Sustr V, Klvana M, Medek P, Biedermannova L, Sochor J, Damborsky J. CAVER 3.0: A tool for the analysis of transport pathways in dynamic protein structures. PLoS Comput Biol. 2012;8(10):e1002708. doi: 10.1371/journal.pcbi.1002708. PubMed DOI PMC

Sehnal D, Svobodova Varekova R, Berka K, Pravda L, Navratilova V, Banas P, Ionescu CM, Otyepka M, Koca J. MOLE 2.0: advanced approach for analysis of biomacromolecular channels. J Cheminformatics. 2013;5(1):39. doi: 10.1186/1758-2946-5-39. PubMed DOI PMC

Yaffe E, Fishelovitch D, Wolfson HJ, Halperin D, Nussinov R. MolAxis: Efficient and accurate identification of channels in macromolecules. Proteins Struct Funct Bioinforma. 2008;73(1):72–86. doi: 10.1002/prot.22052. PubMed DOI PMC

Kozlikova B, Sebestova E, Sustr V, Brezovsky J, Strnad O, Daniel L, Bednar D, Pavelka A, Manak M, Bezdeka M, Benes P, Kotry M, Gora A, Damborsky J, Sochor J. CAVER Analyst 1.0: graphic tool for interactive visualization and analysis of tunnels and channels in protein structures. Bioinformatics. 2014;30(18):2684–685. doi: 10.1093/bioinformatics/btu364. PubMed DOI

Devaurs D, Bouard L, Vaisset M, Zanon C, Al-Bluwi I, Iehl R, Simeon T, Cortes J. MoMA-LigPath: a web server to simulate protein-ligand unbinding. Nucleic Acids Res. 2013;41(Web Server issue):297–302. doi: 10.1093/nar/gkt380. PubMed DOI PMC

Isralewitz B, Gao M, Schulten K. Steered molecular dynamics and mechanical functions of proteins. Curr Opin Struct Biol. 2001;11(2):224–30. doi: 10.1016/S0959-440X(00)00194-9. PubMed DOI

Ludemann SK, Lounnas V, Wade RC. How do substrates enter and products exit the buried active site of cytochrome P450cam? 1. Random expulsion molecular dynamics investigation of ligand access channels and mechanisms. J Mol Biol. 2000;303(5):797–811. doi: 10.1006/jmbi.2000.4154. PubMed DOI

Dodge S, Weibel R, Lautenschütz AK. Towards a taxonomy of movement patterns. Inf Vis. 2008;7(3):240–52. doi: 10.1057/PALGRAVE.IVS.9500182. DOI

Andrienko G, Andrienko N, Bak P, Keim D, Wrobel S. Visual Analytics of Movement. Heidelberg: Springer; 2013.

Vrotsou K, Janetzko H, Navarra C, Fuchs G, Spretke D, Mansmann F, Andrienko N, Andrienko G. SimpliFly: A methodology for simplification and thematic enhancement of trajectories. IEEE Trans Vis Comput Graph. 2015;21(1):107–21. doi: 10.1109/TVCG.2014.2337333. PubMed DOI

Bidmon K, Grottel S, Bös F, Pleiss J, Ertl T. Visual Abstractions of Solvent Pathlines near Protein Cavities. Comput Graph Forum. 2008;27(3):935–942. doi: 10.1111/j.1467-8659.2008.01227.x. DOI

Luboschik M, Maus C, Schulz HJ, Schumann H, Uhrmacher A. Heterogeneity-based guidance for exploring multiscale data in systems biology. In: Proceedings of the IEEE Symposium on Biological Data Visualization (BioVis’12). IEEE: 2012. p. 33–40.

Phillips M, Georgiev I, Dehof AK, Nickels S, Marsalek L, Lenhof HP, Hildebrandt A, Slusallek P. Measuring properties of molecular surfaces using ray casting. In: Parallel Distributed Processing, Workshops and Phd Forum (IPDPSW), 2010 IEEE International Symposium On. IEEE: 2010. p. 1–7.

Lindow N, Baum D, Hege HC. Voronoi-based extraction and visualization of molecular paths. IEEE Trans Vis Comput Graph. 2011;17(12):2025–034. doi: 10.1109/TVCG.2011.259. PubMed DOI

Parulek J, Turkay C, Reuter N, Viola I. Implicit surfaces for interactive graph based cavity analysis of molecular simulations. In: Biological Data Visualization (BioVis), 2012 IEEE Symposium On. IEEE: 2012. p. 115–22.

Parulek J, Turkay C, Reuter N, Viola I. Visual cavity analysis in molecular simulations. BMC Bioinforma. 2013;14(Suppl 19):4. doi: 10.1186/1471-2105-14-S19-S4. PubMed DOI PMC

Lindow N, Baum D, Bondar AN, Hege HC. Exploring cavity dynamics in biomolecular systems. BMC Bioinforma. 2013;14(S-19):5. doi: 10.1186/1471-2105-14-S19-S5. PubMed DOI PMC

Krone M, Reina G, Schulz C, Kulschewski T, Pleiss J, Ertl T. Interactive extraction and tracking of biomolecular surface features. Comput Graph Forum. 2013;32(3pt3):331–40. doi: 10.1111/cgf.12120. DOI

Kozlikova B, Jurcik A, Byska J, Strnad O, Sochor J. Visualizing movements of protein tunnels in molecular dynamics simulations. In: Eurographics Workshop on Visual Computing for Biology and Medicine, VCBM 2014, Vienna, Austria, 2014. Proceedings: 2014. p. 97–106. http://dx.doi.org/10.2312/vcbm.20141188. DOI

Byska J, Le Muzic M, Groeller ME, Viola I, Kozlikova B. AnimoAminoMiner: Exploration of protein tunnels and their properties in molecular dynamics. IEEE Trans Vis Comput Graph. 2016;22(1):747–56. doi: 10.1109/TVCG.2015.2467434. PubMed DOI

Savitzky A, Golay MJ. Smoothing and differentiation of data by simplified least squares procedures. Anal Chem. 1964;36(8):1627–39. doi: 10.1021/ac60214a047. DOI

Visvalingam M, Whyatt JD. Computer Graphics Forum, vol. 9. Oxford: Blackwell Publishing Ltd; 1990. The Douglas-Peucker algorithm for line simplification: Re-evaluation through visualization.

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...