MolAxis is a tool for the identification of high clearance pathways
or corridors which represent molecular channels in the complement
space of proteins.
It is extremely efficient because it samples the medial axis of the
complement of the molecule, reducing the problem dimension to two,
since the medial axis is composed of surface patches. It is designed
to analyze proteins channels, calculate pore dimensions and analyze
atom accessibility. MolAxis reads files in the standard Protein Data
Bank format (PDB) containing a single frame or multiple frames generated
by molecular dynamics (MD) simulations.
| MolAxis handles two distinct scenarios: It computes channels
that connect a single point (like an inner chamber) to the bulk
solvent, and it also computes transmembrane (TM) channels. MolAxis has
a friendly web interface (see the Web Server tab).
It also has a stand-alone version, statically compiled for linux,
which can be downloaded from the Download tab. |
We give here a high level description of the algorithm. The algorithm
employs computational geometry techniques. Full details of the theory
and the algorithm are given in the thesis cited in the reference
section below. The algorithm is composed of the following steps:
In case the molecule is a transmembrane molecule, the source point is
defined to be at infinity. In that case, the reported channel is a
concatenation of two paths in the corridor tree, which pass through a
user-defined sphere, and the reach the bounding sphere in two opposite
We approximate the molecule using a collection of fixed-size
balls. The number of balls needed depends on the required quality of
the approximation. In the extreme case, where the user is interested
in a low resolution, each atom is approximated using a single ball.
We compute the Voronoi diagram of the centers of the fixed-sized
balls. We intersect the diagram with a user-defined bounding
sphere. This defines our area of interest.
We discard the parts of the Voronoi diagram that intersect the molecule.
We define a graph, using the Voronoi vertices and edges. We give a
weight to each edge that depends on its length and on its distance
from the surface of the molecule.
We define a source point (root vertex). The user can either supply a
source point or allow MolAxis to automatically choose the source point
to be the center of the largest chamber in the molecule.
We apply a shortest path optimization algorithm (Dijktra's algorithm)
on the graph, computing a tree we call the corridor tree.
The desired channels are paths in the corridor tree. We avoid
reporting duplicate channels by using the split distance
parameter. The split distance bounds the distance to the least common ancestor of the channel and all previously reported channels.
|Figure 1: CYP3A4 channels as detected by
MolAxis. CYP3A4 is represented by cartoons and the heme prosthetic
group is represented by its VDW surface and colored orange. Each
channel surface is colored in a different color for the sake of
A short list of the tool features include:
- Finding channels that connect a
chamber to the bulk solvent.
- Finding transmembrane channels.
- Graphical display of channels, using
- Channel properties, such as dimension and lining residues.
- Supports a web interface and a stand-alone native linux version.
- Highly accurate and efficient. Robust due to the use of the CGAL library.
The authors request that all published work which utilizes MolAxis
include at least the citation of the paper "MolAxis: A server for
Identification of Channels in Macromolecule", as given below.
Description of the MolAxis algorithms:
Eitan Yaffe, Dan Fishelovitch, Haim J. Wolfson, Dan Halperin, Ruth Nussinov. "MolAxis: Efficient and Accurate Identification of Channels in Macromolecules." PROTEINS: Structure, Function, and Bioinformatics. Volume 73, Issue 1, October 2008, Pages: 72-86 [link]
Description of the MolAxis webserver:
Eitan Yaffe, Dan Fishelovitch, Haim J. Wolfson, Dan Halperin, Ruth Nussinov. "MolAxis: A server for Identification of Channels in Macromolecule". Nucleic Acids Research. Volume 36 (Web Server issue), 1 July 2008, Pages: W210-W215. [link].
Analysis of computational geometry properties of the MolAxis algorithm:
Eitan Yaffe, Dan Halperin. "Approximating the Pathway Axis and the Persistence Diagram of a Collection of Balls in 3-Space". Symposium on Computational Geometry (SoCG '08).
M.Sc. thesis of Eitan Yaffe:
Eitan Yaffe. "Efficient Construction of Pathways in the Complement of the Union of Balls in R3". MSc. Thesis, Tel-Aviv University, September 2007.