MolAxis: Efficient and accurate identification of channels in macromolecules (original) (raw)
Related papers
MolAxis: a server for identification of channels in macromolecules
Nucleic Acids Research, 2008
MolAxis is a freely available, easy-to-use web server for identification of channels that connect buried cavities to the outside of macromolecules and for transmembrane (TM) channels in proteins. Biological channels are essential for physiological processes such as electrolyte and metabolite transport across membranes and enzyme catalysis, and can play a role in substrate specificity. Motivated by the importance of channel identification in macromolecules, we developed the MolAxis server. MolAxis implements state-of-the-art, accurate computational-geometry techniques that reduce the dimensions of the channel finding problem, rendering the algorithm extremely efficient. Given a protein or nucleic acid structure in the PDB format, the server outputs all possible channels that connect buried cavities to the outside of the protein or points to the main channel in TM proteins. For each channel, the gating residues and the narrowest radius termed 'bottleneck' are also given along with a full list of the lining residues and the channel surface in a 3D graphical representation. The users can manipulate advanced parameters and direct the channel search according to their needs. MolAxis is available as a web server or as a stand-alone program at http://bioinfo3d.cs.tau.ac.il/MolAxis.
2016
MolAxis is a freely available, easy-to-use web server for identification of channels that connect buried cavities to the outside of macromolecules and for transmembrane (TM) channels in proteins. Biological channels are essential for physiological processes such as electrolyte and metabolite transport across membranes and enzyme catalysis, and can play a role in substrate specificity. Motivated by the importance of channel identification in macromolecules, we developed the MolAxis server. MolAxis implements state-of-the-art, accurate computational-geometry techniques that reduce the dimensions of the channel finding problem, rendering the algorithm extremely efficient. Given a protein or nucleic acid structure in the PDB format, the server outputs all possible channels that connect buried cavities to the outside of the protein or points to the main channel in TM proteins. For each channel, the gating residues and the narrowest radius termed 'bottleneck' are also given along with a full list of the lining residues and the channel surface in a 3D graphical representation. The users can manipulate advanced parameters and direct the channel search according to their needs. MolAxis is available as a web server or as a stand-alone program at http://bioinfo3d.cs.tau.ac.il/MolAxis.
MOLE: a Voronoi diagram-based explorer of molecular channels, pores, and tunnels
Structure, 2007
We have developed an algorithm, ''MOLE,'' for the rapid, fully automated location and characterization of molecular channels, tunnels, and pores. This algorithm has been made freely available on the Internet (http://mole.chemi. muni.cz/) and overcomes many of the shortcomings and limitations of the recently developed CAVER software. The core of our MOLE algorithm is a Dijkstra's path search algorithm, which is applied to a Voronoi mesh. Tests on a wide variety of biomolecular systems including gramicidine, acetylcholinesterase, cytochromes P450, potassium channels, DNA quadruplexes, ribozymes, and the large ribosomal subunit have demonstrated that the MOLE algorithm performs well. MOLE is thus a powerful tool for exploring large molecular channels, complex networks of channels, and molecular dynamics trajectories in which analysis of a large number of snapshots is required.
MOLEonline 2.0: interactive web-based analysis of biomacromolecular channels
Nucleic acids research, 2012
Biomolecular channels play important roles in many biological systems, e.g. enzymes, ribosomes and ion channels. This article introduces a web-based interactive MOLEonline 2.0 application for the analysis of access/egress paths to interior molecular voids. MOLEonline 2.0 enables platform-independent, easy-to-use and interactive analyses of (bio)macromolecular channels, tunnels and pores. Results are presented in a clear manner, making their interpretation easy. For each channel, MOLEonline displays a 3D graphical representation of the channel, its profile accompanied by a list of lining residues and also its basic physicochemical properties. The users can tune advanced parameters when performing a channel search to direct the search according to their needs. The MOLEonline 2.0 application is freely available via the Internet at http://ncbr.muni.cz/mole or http://mole.upol.cz.
Geometrical Detection of Pathways in Protein Structures Leading Among More Binding Sites
In this paper, we present a novel algorithm for the detection of pathways connecting two or more specific user defined binding sites, which are deeply buried in a protein macromolecule. These pathways can play an important role in the protein reactivity and overall behavior. However, our new algorithm can be generalized and used for computation of pathways inside an arbitrary set of spheres in three-dimensional space, leading through an ordered set of user-defined sites. Our approach is based on the localized Voronoi diagram approach and the Delaunay triangulation. The greatest benefit of our approach is its independence on the size of the input data set. This is achieved by using only a subset of all atoms in the macromolecule in each phase. This substantially reduces the size of the processed space. The method can also be utilized for determination whether pathways wide and straight enough exist among determined binding sites. This information then serves as the guideline for assessing the migration of products of chemical reaction between these binding sites.
Chanalyzer: A Computational Geometry Approach for the Analysis of Protein Channel Shape and Dynamics
Frontiers in Molecular Biosciences
Morphological analysis of protein channels is a key step for a thorough understanding of their biological function and mechanism. In this respect, molecular dynamics (MD) is a very powerful tool, enabling the description of relevant biological events at the atomic level, which might elude experimental observations, and pointing to the molecular determinants thereof. In this work, we present a computational geometry-based approach for the characterization of the shape and dynamics of biological ion channels or pores to be used in combination with MD trajectories. This technique relies on the earliest works of Edelsbrunner and on the NanoShaper software, which makes use of the alpha shape theory to build the solvent-excluded surface of a molecular system in an aqueous solution. In this framework, a channel can be simply defined as a cavity with two entrances on the opposite sides of a molecule. Morphological characterization, which includes identification of the main axis, the corresp...
CHEXVIS: a tool for molecular channel extraction and visualization
BMC Bioinformatics, 2015
Background: Understanding channel structures that lead to active sites or traverse the molecule is important in the study of molecular functions such as ion, ligand, and small molecule transport. Efficient methods for extracting, storing, and analyzing protein channels are required to support such studies. Further, there is a need for an integrated framework that supports computation of the channels, interactive exploration of their structure, and detailed visual analysis of their properties. Results: We describe a method for molecular channel extraction based on the alpha complex representation. The method computes geometrically feasible channels, stores both the volume occupied by the channel and its centerline in a unified representation, and reports significant channels. The representation also supports efficient computation of channel profiles that help understand channel properties. We describe methods for effective visualization of the channels and their profiles. These methods and the visual analysis framework are implemented in a software tool, CHEXVIS. We apply the method on a number of known channel containing proteins to extract pore features. Results from these experiments on several proteins show that CHEXVIS performance is comparable to, and in some cases, better than existing channel extraction techniques. Using several case studies, we demonstrate how CHEXVIS can be used to study channels, extract their properties and gain insights into molecular function. Conclusion: CHEXVIS supports the visual exploration of multiple channels together with their geometric and physico-chemical properties thereby enabling the understanding of the basic biology of transport through protein channels. The CHEXVIS web-server is freely available at http://vgl.serc.iisc.ernet.in/chexvis/. The web-server is supported on all modern browsers with latest Java plug-in.
Identifification of Substrate Channels and Protein Cavities
Journal of Molecular Modeling, 1998
A grid-based algorithm is presented for identifying and displaying channels and cavities in a given protein structure. A point on a regular Cartesian grid is defined to be located in a cavity or a channel if the point has neighbouring grid points in the direction of at least two Cartesian axes, which are located inside the molecule. The cavities or channels can be displayed as clusters of these grid points or as the part of the surface and the amino acid residues lying next to these grid points. The algorithm was tested successfully using the gramicidin A dimer, different cytochrome P450's, and the proteolytic enzyme trypsin.