MotiveValidator

Statement of purpose

The advancement of research in structural biology has provided a large body of structural data deposited in various databases. One great example is the Protein Data Bank (PDB), which has been growing exponentially, and which currently consists of more than 100,000 structures of biomolecules and their complexes. Such large bodies of data, especially accumulated over a short period of time and using high throughput techniques, will inherently be plagued by a variety of problems.

Validation arose as a major issue in the structural biology community when it became apparent that some published structures contained serious errors, either documented (e.g., due to insufficient electron density in a certain area), or not. Structural databases generally require that the new submissions be checked prior to acceptance. The tools employed for presubmission validations work fairly well for well studied residues like amino acids or nucleotides. However, an essential step in the validation process is checking the ligand structure, because ligands play a key role in protein function, and also because they are the main source of errors in structures. A notable case of ligand validation is the analysis of carbohydrate structures, because they have complex topology and many chiral atoms. Yet carbohydrates are involved in a variety of fundamental biological processes and they have large pharmaceutical and diagnostic potential. Additionally, more than 60% of nontrivial-sized ligands (> 10 atoms) from the Protein Data Bank contain a carbohydrate. In recent years, many algorithms for validation, ligand validation and carbohydrate validation have been developed. Nonetheless, significant limitations persist, such as insufficient coverage of ligands and time inefficiency (i.e., calculations are time demanding and only one entry can be validated in each run).

We have developed MotiveValidator, a user-friendly, interactive and platform independent environment for the speedy validation of ligands, residues and fragments (denoted as structural motifs). MotiveValidator covers all standard and custom residues and ligands, and was successfully tested in six research labs on more than 50.000 input samples.

Availability and technical details

Where to find MotiveValidator

MotiveValidator is freely available via the internet since September 2013 at our webpages. There is no login requirement for using MotiveValidator.

What you need in order to run MotiveValidator

• Up to date internet browser with WebGL support. Check it out, if your browser is compliant.
• JavaScript enabled.

How to get around the web page

For the quick tour on using MotiveValidator service, please click the Guide button in the upper right corner and follow instructions.

Input file requirements

Before you move on, please consult the Terminology used within the MotiveValidator.

MotiveValidator is meant for residue based validations against LigandExpo<ref name="Lutteke_2004"/> models, and thus accepts input files in PDB format<ref name="pdb"/>. The PDB format is necessary due to the fact that it contains residue information (the 3-letter code residue name and residue identifier). However, especially in the case of more unusual residues or user defined motifs, it is many times useful to also submit your structures in SD/SDF/MOL format along with the PDB format. This is to insure that MotiveValidator identifies inter-atomic bonds correctly. Additionally, since the representation of large biomacromolecules and their complexes is moving towards a more general format, MotiveValidator also allows to upload the structure to be validated in PDBx/mmCIF format.

The PDB file format is well established. The following fields must appear correctly in your input PDB files: atom index, atom name, element symbol, residue name, residue index, 3D coordinates. Alternate locations of atoms are ignored. If MotiveValidator finds any issues in the input files, it will report them as warnings or processing errors TODO link na detaily.

References

<references> <ref name="Lutteke_2004">Lütteke,T. and von der Lieth,C.-W. (2004) pdb-care (PDB carbohydrate residue check): a program to support annotation of complex carbohydrate structures in PDB files. BMC Bioinformatics, 5, 69.</ref>

<ref name="pdb">Read more about the PDB format at http://wwpdb.org/documentation/format33/v3.3.htm</ref> </references>