Category Proteomics>Protein Structure/Modeling Systems/Tools

Abstract SPACE is a suite of tools for protein (Structure Prediction and Analysis based on Complementarity and Environment).

This server includes tools for predicting and analyzing structures of biomolecules and their complexes. The manufacturer’s approach is based on surface complementarity (shape and chemical compatibility) of interacting surfaces.

The major body of the suggested tools consists of a set of servers and programs:

1) The servers provide: analysis of Ligand-Protein Contacts and Contacts of Structural Units (LPC/CSU); structural analysis of point mutations (MutaProt); Side Chain modeling (SCCOMP);

Building the crystal environment of a given Protein Data Base (PDB) file and the analysis of Crystal Contacts (CryCo); Contact Map Analysis (CMA); and predicting transition metal-binding sites using protein structure (CHED) or Sequence data (SeqCHED).

2) The programs include: molecular docking (LIGIN); Ligand-Protein Contact analysis (LPC); Analysis of Contact of Structural Units in biomolecules (CSU); Side Chain modeling (SCCOMP).

The output of LPC and CSU is in a simple text format and it can be used as input to additional programs in order to answer potential end-user questions.

A shared feature of all SPACE tools is the application of the LPC/CSU definition for inter-atomic contacts and surface complementarity. Inter-atomic contacts are calculated either numerically or analytically. Complementarity is estimated based on the deviation of atoms into eight (8) classes according to their physicochemical properties.

LPC/CSU - contact analysis of biomolecules -- The LPC/CSU server analyzes and visualizes (either with the Chime plug-in or the Java based Jmol) atomic interactions within a protein or protein complex, including resolved water molecules and attached ligands, and nucleic acids.

Different levels of analysis can be chosen: contacts can be grouped and sorted by atom, residue or contact type (H-bond, hydrophobic-hydrophobic and aromatic-aromatic). The output provides characteristics for every atom-atom contact (atom properties, distance, and contact area).

CryCo - analysis of crystal contacts -- The CryCo server builds coordinate files in a PDB format for the unit cell as well as for the complete crystal environment of one molecule. The structural environment is built in several steps.

First, symmetry related molecules are created using the PDBSET program from the CCP4 suite. When necessary, all molecules are translocated to one unit cell. The 26 adjacent cells in the crystal lattice are then constructed by translation and any atom farther than a chosen threshold from the closest atom of the central molecule is removed.

Detailed analyses of atomic contacts are based on CSU software. Interactive visualization options and coordinate output files are provided and an option to submit a structural file for analysis is also provided.

CryCo differs from existing tools such as the WHAT IF web server and the xpack VRML-based program in providing visualization options, detailed contact analyses and several files with new features for downloading.

CMA - contact map analysis -- For a given PDB file, the ‘Contact Map Analysis’ server (CMA) evaluates residue-residue contacts between two chains or within a single one. In an example illustration (Not shown here...), the interface contacts between chains L and H in PDB file 1DLF are considered.

Residue-residue contacts are represented as an interactive contact map, where a square at the crossing of two residues indicates a contact. Positioning the cursor over the square; highlights summary information about the contacting residues and their total contact area.

Clicking on the square reveals a table with more detailed contact information based on LPC/CSU software, including names of the contacting atoms, distances and atom-atom contact areas. Links for analysis and visualization of contact residues are likewise provided.

The CMA server was extensively used to analyze inter domain contacts in sandwich-like proteins. It differs from existing servers, such as WebMol, iMolTalk and Stride, by providing detailed visualization and detailed contact analysis.

MutaProt - structural rearrangements upon point mutations -- MutaProt contains a database of pairs of PDB files whose members differ in one or two amino acids. The software examines the microenvironment of the mutated residues. The database is accessed by specifying a PDB file, keyword or a pair of amino acids.

Accessibility and atomic contacts of the mutated residue are provided by CSU software. The current version of the server has a number of significant improvements. MutaProt now extracts pairs based on differences at the chain level. This dramatically increases the database to ~200,000 pairs.

Wild-type structures are distinguished from mutant ones where information is available. An option has been included for the user submission of a structural file for pairing up with PDB entries and MutaProt analysis.

The interactive graphics have been expanded to include the entire PDB structure and presentation of the protein sequence is included along with secondary structure assignment based on DSSP.

In addition, superposition of the two (2) pair members is now done analytically. A list of publicly available mutation databases is provided. MutaProt is unique in providing detailed on-line analysis of atomic contacts and offering a superimposed 3D presentation of regions being compared.

SCCOMP - side chain modeling -- SCCOMP is a server for side chain modeling. It uses a scoring function that includes terms for complementarity (CSU definitions of geometric and chemical compatibility), excluded volume, internal energy based on rotamer probability and solvent accessible surface.

The input is a coordinate file in the PDB format with or without side chain coordinates. The output is a file with predicted coordinates for side chains.

SCCOMP has an accuracy of 92-94% for correct Chi1 prediction (± 40°) of buried residues, 82-84% for all residues, and about 1.7 Å for overall root mean squared difference (rmsd) (Not including Cß). The exact values depend on the searching procedure.

A fast iterative search, takes about a minute on the web server for a typical protein. A slower stochastic method takes about 12 minutes and improves the prediction by about 2% and 0.1 Å rmsd.

SCCOMP also permits:

1) Modeling only a subset of residues;

2) Performing any number of mutations; and

3) Using a homologous structure as a template.

Note: At the manufacturer’s web-site you can download the source code for SCCOMP for different Unix/Linux platforms. You can also use their web server for modeling. The results are sent back to you via E-mail.

CHED server for predicting soft metal binding sites in proteins -- The CHED server uses the “CHED” algorithm to predict 3D intra-chain protein binding sites for transition metals (Zn, Fe, Mn, Cu, Ni, Co, and Ca and Mg sites that can be replaced by a transition metal).

The algorithm searches for a triad of amino acids composed of 4 residue types (Cys, His, Glu, Asp) having ligand atoms within specific distances. It allows one target residue to rotate in rotamer space, taking into account structural rearrangements that may occur upon metal binding. A binding site is considered to be true if one or more correct amino acid ligands have been predicted.

Machine learning algorithms are used to filter out false positives -

MILD FILTER - based on the frequency of hits, yields high sensitivity (depending on metal type, 70-100% of apo sites are captured, with predictions statistically accurate in 50-70% of the cases).

STRINGENT FILTER - using decision tree and support vector machine (SVM) technology, yields high selectivity (depending on metal type, 45-85% of apo sites are captured with predictions statistically accurate in 85-100% of the cases).

SeqCHED Server - Predict soft metal binding sites using sequence data --

This web-tool enables the user to analyze a translated gene sequence for soft (Zn, Fe, Ni, Cu, Co, Mn), and promiscuous hard (Mg, Ca), metal-ion binding sites. The application checks for homology of your target sequence to PDB template sequences and then models the target side chains in 3D (using SCCOMP - see above...) on the backbone of the selected template.

A metal binding prediction algorithm (based on the CHED procedure see above...) is then applied to the 3D model to identify any putative binding sites and their ligating CHED (Cys, His, Glu, Asp) residues.

LIGIN - Software for molecular docking using surface complementarity --

LIGIN has been created and is currently being developed for searching for ligand binding sites in biomolecular structures. It locates binding modes for a specified ligand of known 3D structure in a target protein and ranks these modes/ligand positions according to a simple function.

The main premise is that an effective ligand binding site should provide a large, attractive contact surface for its ligand. This is assessed by the contact surface between atoms and a complementarity function.

The complementarity function is a simple sum of surface areas of atomic contacts with weight plus or minus one depending on the types of atoms in contact, and one term which prevents strong atomic bumping during searching.

In order to find the binding site, the program performs two (2) steps. Firstly, it maximizes the complementarity function as a function of the ligand position in the space of 6 parameters, considering the ligand as a rigid body. Because of the multiple-maxima problem, the program starts the search for the global maximum from a set of random points in 6- dimensional space.

At the second step, the program optimizes the lengths of the possible hydrogen bonds. For this, the program starts from structures obtained in the first step and optimizes the lengths of the appropriate and already existent hydrophilic contacts.

SPACE programs available -- The following programs can be downloaded from the manufacturer’s web-site:

1) LIGIN - Software for molecular docking using surface complementarity;

2) LPC - Software for Ligand-Protein Contacts (LPC) analysis;

3) CSU - Software for analysis of Contact of Structural Units (CSU) in proteins; and

4) SCCOMP - Software for side chain modeling in proteins (as stated above...).

System Requirements

Contact manufacturer.


Manufacturer Web Site SPACE

Price Contact manufacturer.

G6G Abstract Number 20730

G6G Manufacturer Number 104294