To avoid erroneous structural models, various methods have been developed for protein structure validation. One such method verifies the model's agreement with the original experimental data or a subset which has not been used for model building. Another set of methods, the so-called knowledge-based methods, examine the geometry, stereochemistry and other structural properties of the model independently from the original data. This latter set of methods reports the extent to which the parameters of the analyzed structure fit within the range of values observed in previously solved high-resolution structures.
For optimum performance, several different methods should be used before the structural model can be regarded as validated and assumed error-free. Knowledge-based methods for protein structure validation typically require the full-atom Protein Data Bank PDB -formatted file of protein structure as input, and present the output as a list of confidence values associated with each amino acid or each atom.
Poorly modeled amino acids frequently occur in regions close in space, which may be distant at the primary sequence level. The graphical presentations of results reported by all structure validation programs are limited to plotting the confidence values against the position in the polypeptide. This output does not allow for the inspection of sites of potential errors at the level of the 3D structure.
A very useful feature of COLORADO3D is its ability to visualize, in color, potential errors in protein structures derived from either experimental analysis or modeling , regions buried in the protein core and inaccessible to the solvent, and regions of high sequence conservation.
Some of the third-party components including PROSAII and VERIFY3D may be unavailable for commercial users, who are nevertheless welcome to contact us to obtain a separate, but limited, license or to obtain a stand-alone version of the program without the third-party components. All T-factors are linearly scaled to a range between By default, residues with high scores good structure, highly conserved, deeply buried will be colored in blue low T-factor and residues with low scores poor structure, variable, exposed will be colored in red high T-factor.
The intermediate values will range from green to yellow to orange. VERIFY3D operates on the 3D—1D profile of a protein structure proposed by Eisenberg and co-workers 6 , which includes the statistical preferences for the following criteria: i the area of the residue that is buried; ii the fraction of side-chain area that is covered by polar atoms oxygen and nitrogen ; iii the local secondary structure.
For structures determined by X-ray crystallography, the default option in VERIFY3D is to assess the compatibility of each amino acid residue with the local 3D structure by averaging the 3D—1D score in a window of 21 residues. For protein models, however, we found that the best results are obtained when a shorter window range of 5—11 residues is used.
Scores reported by ANOLEA combine a pairwise distance-dependent non-local energy term with an accessible surface energy term. All individual structures will be validated and colored separately. As already mentioned, this analysis allows for the identification of regions of dubious or unusual structure that may not necessarily be adjacent at the amino acid sequence level, but that are adjacent at the 3D structure level. Comparison of different structures, such as alternative models of the same protein, can greatly facilitate the choice of optimal fragments or versions and, hence, can greatly facilitate the refinement of protein structures.
Two alternative homology models of a protein experimentally solved structure deposited as 1h7m in the Protein Data Bank , colored according to the results of structure evaluation using the VERIFY3D method. Right panel: the model has been corrected amino acids of one helix were shifted along the polypeptide by one residue, thereby increasing one loop and shortening the other, and changing the interactions of the side-chains with the rest of the protein , leading to the improvement of scores for the suspicious region.
The latter model turned out to be indeed correct. In addition to submitting a PDB file, users can also optionally include a multiple alignment of homologous sequences, starting with the query sequence.
In this case, additional structural models will be generated based on the backbone of the query, with amino acid substitutions modeled by SCWRL 11 according to the equivalencies of residues obtained from the multiple sequence alignment. This analysis allows for the verification of the multiple sequence alignment with the structural requirements of the protein fold and correction of errors in the alignment, if necessary. The accessible surface area is a parameter widely used in the analysis of protein structure and stability.
However, it does not distinguish between atoms immediately below the protein surface and atoms in the core of the protein.
The method can be simply described as an estimation of the burial of the hydrophobic surface area. The residue depth parameter is believed to correlate better than accessibility with the effects of mutations on protein stability and on protein—protein interactions.
The depth of a residue is the average of the constituent atom depths. In addition to the visualization of calculated protein structure features, COLORADO3D also allows users to take advantage of structural information to analyze the sequence information in a 3D context. To color the protein structure according to the degree of sequence conservation, the user must submit a single PDB-formatted structure a template and a multiple sequence alignment starting with the template sequence. For each column of the alignment, the amino acid percentage identity i.
Using COLORADO3D to color the structure by sequence conservation can greatly facilitate the identification of conserved patches on the protein surface, which may correspond to functionally important sites such as catalytic centers in enzymes. Verifi3D provides a flexible reporting function which can create reports collating all the results from all the verification tests run.
Instances of clashes are logged and tagged to the components in the model. Clicking on the report moves the 3D view to each one for visual checking of issues. This is handled within the Verifi3D cloud. The Pathfinding function will find the shortest path between one or more points in the model, routing around objects. This can be used to find the nearest emergency exit from any point of the imported building model.
It can also check for headroom on staircases. Once the analysis is done, these paths are visible within in the model. Beyond clash detection and pathfinding, Verifi3D offers a seriously impressive number of ways to slice, dice, search and compare model components in context. Validation checks can be run on object properties, object parameters and on the metadata of classifications, categories and families, with the results shown automatically within the viewer.
This is great for seeing how many tagged objects of specific types are included, e. Components can be tagged and measured within the application; tagged items can be shared with the project team. This is a quick way to run through a number of repetitive visual checks, as you would do for fire safety. Verifi3D is very much a development tool for creating model validation checks which suit various workflows.
This could be anything from one specific rule or rulesets, made up from multiple rules and checked simultaneously. These can be written to compare against project-specific requirements or against object properties, classifications, families and parameters. As Unity offers a nice looking and fast real-time environment, it would be a shame to not use it for some visualisation.
Currently, there are some seriously big players using the software and assisting in its rapid development — namely Takenaka, BuroHappold Engineering and TBI.
Now that the platform has been officially launched, Xinaps can concentrate on adding additional vertical functionality. No problem. Share a few details, and we'll get you an answer right away. Your information has been sent and we will send you a response right away.
Power and Utilities. Oil and Gas. Civil Engineering. Line separator. Experienced 3D Scanning Professionals.
0コメント