MUSTANG-MR structural sieving server: applications in protein structural analysis and crystallography

Area of Science:

• Structural Biology
• Computational Biology
• Bioinformatics

Background:

• Related proteins with similar functions often exhibit structural similarities.
• Molecular sieving is a process used to identify common structural cores among multiple protein structures.
• Existing methods for analyzing protein structures can be enhanced by improved structural alignment techniques.

Purpose of the Study:

• To develop a novel web server for molecular sieving of protein structures.
• To improve the identification of structurally conserved regions of functional importance.
• To facilitate protein structure determination using molecular replacement.

Main Methods:

• Utilized the MUSTANG multiple structural alignment program.
• Developed an iterative filtering process to refine residue-residue correspondences and remove poorly fitting structures.
• Generated Lesk-Hubbard graphs to visualize structurally conserved regions based on RMSD and residue correspondences.

Main Results:

• The web server generates 'sieved' models by optimizing structural superpositions.
• Iterative filtering enhances the identification of structurally conserved cores, such as active sites.
• Lesk-Hubbard graphs effectively highlight conserved regions, showing linear trends for cores and exponential trends for divergent regions.

Conclusions:

• The developed application addresses the challenge of identifying common substructures among related proteins for function prediction.
• The generated sieved models have practical applications in protein crystallographic structure determination via molecular replacement.