Investigating Macro-Molecular Interfaces with Intervor

Protein - Protein; Protein - Nucleic Acid; Protein - Drug

PROBLEM SPECIFICATION

Given a macro-molecular complex featuring two partners and possibly water molecules, an interface between these partners is defined as a collection of Voronoi faces separating them; equivalently, each facet identifies two interface atoms. See the bibliography below for a precise description of the interface. The goal of Intervor is to:

detect interface atoms, as well as water molecules squeezed in-between the partners;
provide a description of the Voronoi interface in terms of patches, surface area, curvature, atomic composition;
qualify interface atoms and Voronoi tiles as a function of their depth at the interface.

Addditional notes:

Intervor is based on the Triangulation_3 and Alpha_shape_3 packages of the Computational Geometry Algorithms Library.
The atomic radii used are the so-called group radii from Chothia and Janin, Nature 256, 1975. Details here.

BIBLIOGRAPHY

Algorithms

[C10] Revisiting the Voronoi description of protein - protein interfaces: algorithms; F. Cazals; Pattern Recongnition in Bioinformatics, 2010.

Structural studies

[CPBJ06] Revisiting the Voronoi description of Protein-Protein interfaces; F. Cazals, F. Proust, and R. Bahadur, J. Janin; Protein Science, 15 (9), 2006.
[BGNC09] Shelling the Voronoi interface of protein-protein complexes reveals patterns of residue conservation, dynamics and composition; Bouvier and R. Grunberg and M. Nilges and F. Cazals; Proteins: Structure, Function, and Bioinformatics, 76(3), 2009.

Software

[CL10] Modeling macro-molecular interfaces with Intervor; S. Loriot and F. Cazals; Bioinformatics 26 (7); 2010.
Also available as INRIA Tech Report .

Misc

[TTCG99] The packing density in proteins: standard radii and volumes. J. Tsai, R. Taylor, C. Chothia, and M. Gerstein. Journal of Molecular Biology, 290(1):253-266, 1999.

INSTRUCTIONS

1. Provide a PDB file, with extension .pdb or .PDB
2-3. Specify each partner in the complex, as a collection of capital letters identifying the chains. If two or more chains, do not insert blanks in between letters
4. Click Discard water molecules if you wish to drop all water crystallographic water molecules
5. If you wish to discard only water molecules whose temperature factor is too high, provide its value, in the range 0..100
6a-b. Click Filter large Voronoi facets with M if you wish to discard potential large Voronoi facet. If so, provide a value M, in the range 0..100
7. By default, Voronoi facets are colored by the interaction type corresponding to the two atoms defining the facet. Clicking the check-box makes the coloring scheme depend upon the shelling order of the facet.
8. Upon completion, the server will provide you with a link to a zipped tar file containing the results of the calculation. See Modeling macro-molecular interfaces with Intervor; INRIA Tech report 7069; for a detailed description of the result.

Important notes:

Calculations are based upon the following classification of atoms and residues, see [TTCG99]. In particular, hydrogen atoms are discarded.
This web server requires all occupancy factors to be equal to 1. If not and for a more ellaborate processing, the user should retrieve the binary executable, learn about the strategies offered in case of factors < 1, and proceed accordingly.
In case of alternates, the first occurance is the one selected.

RUNNING A CALCULATION

Please send comments / error reports / wishes to abs-software@lists-sop.inria.fr If you use Intervor for a publication, please notify us at abs-software@lists-sop.inria.fr

DOWNLOADING THE EXECUTABLE

Important notes:

Conditions: Free for use in academia, and subject to commercial license for other use.
To see all options available, run the program as intervor.exe --help.

Download page here (authentification requested)

Using Intervor within VMD

The plugin Intervor-vmd-plugin allows one to run a calculation and see the result in VMD.

As an alternative, one can (i) run a calculation from the command-line using the binary executable, (ii) generate a vmd file using the vor2vmd.pl perl script available within the Intervor-vmd-plugin bundle, and (iii) load this file within VMD using the Fast load plugin. The bundle provided upon running a calculation from this web site contains the vmd file to be loaded with Fast load.

Help to install the plugins:

See the VMD page for the plugin installation instructions. The header of the plugins files also contain short indications on how to install the plugins.

Using Intervor within PyMOL

The plugin Intervor-pymol-plugin allows one to run a calculation and see the result in VMD. The bundle provided upon running a calculation from this web site contains the pymol file to be loaded within Pymol.

Gallery

Complex 1vfb: Protein - Protein

(a)Side view of complex	(b)Interface and interface water molecules

Complex 1KX5: Protein - Nucleic Acid

(a)Complex DNA - histones, with structural water at the interface	(b)Interface patches

Complex 2ifb: Protein - Drug

Drug trapped in binding site

Contact: abs-software@lists-sop.inria.fr

Web: F. Cazals