Keywords / Key Attributes : Detection of packing anomalies and wrong rotamer assignments in obsoleted structures, Signaling unbalanced partial charges in designed protein interiors, Detection of low intensity diffused errors in main-chain geometrical parameters, Applications in Homology modeling.
Structure validation
is a crucial component not only in protein crystallography but also in model
quality estimation in homology modeling, protein design and de-novo structure
prediction. Recent studies have emphasized on the need to improve existing
validation tools with the rapid growth of protein crystal structures deposited
in the protein data bank. Two key attributes of a correctly determined atomic
model are optimal packing between side-chains and absence of destabilizing
unbalanced electric fields within the interior of a protein molecule. The
complementarity plot (CP) combines them in a single unified measure and is a
sensitive indicator of the harmony or disharmony of interior residues of a
globular protein with regard to the short and long range forces sustaining the
native fold. The plot has previously been demonstrated to be effective in
detecting local regions of suboptimal packing or electrostatics [1]. CP
has now been compiled into a user
friendly validation package and made
available as a standalone suite of programs in the public domain (http://www.saha.ac.in/biop/www/sarama.html) [2]. A set of
scores have now been included in the methodology which gives an estimate
of the probabilities associated with the distribution of points in the plot and
the propensities of specific residues to different degrees solvent exposure.
These scores have been used to detect a wide variety of local and global
structural errors and compared with other standard validation techniques. CP
was found to be effective in discriminating between obsolete structures and
their corresponding upgraded counterparts, detection of wrong rotamer
assignment and in identifying packing anomalies. CP was especially effective in
the detection of low-intensity errors diffused over the entire polypeptide
chain. A special feature of this validation tool is to signal unbalanced
partial charges within protein interiors. Finally, the application of CP in
protein homology modeling and design has been surveyed. The current study clearly indicates that over and above the commonly used
validation techniques, packing and electrostatics should be included separately
in any validation package and thus, CP should be an useful addition in the
already existing repertoire of structure validation tools.
References:
1.
Self-Complementarity
within Proteins: Bridging the Gap between Binding and Folding.
Sankar Basu, Dhananjay Bhattacharyya, and Rahul Banerjee*
Sankar Basu, Dhananjay Bhattacharyya, and Rahul Banerjee*
Biophysical Journal, 2012, 102
(11) : 2605-2614.
Sankar Basu*, Dhananjay Bhattacharyya, and Rahul Banerjee*
Journal of
Bioinformatics and Intelligent Control, 2013, 2 (4) : 321-323.
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