Analysis of Protein Intermolecular Interactions with MAFFT-DASH

Area of Science:

• Structural bioinformatics
• Computational biology
• Protein structure analysis

Background:

• The Database of Aligned Structural Homologs (DASH) facilitates navigation of the Protein Data Bank (PDB) using pre-computed structural alignments.
• Previous work integrated DASH with MAFFT for improved multiple sequence alignment (MSA) accuracy.
• Recent DASH updates allow queries from user-provided protein coordinates.

Purpose of the Study:

• To extend DASH functionality for retrieving intermolecular interactions of structurally similar protein domains.
• To demonstrate the utility of the enhanced DASH tool using a specific protein domain example.

Main Methods:

• Utilizing pre-computed pairwise structural alignments from DASH.
• Integrating DASH with MAFFT for enhanced multiple sequence alignments.
• Developing new DASH query capabilities for user-provided protein coordinates.
• Extending DASH to identify and retrieve intermolecular interactions for structurally similar domains.

Main Results:

• The extended DASH successfully retrieves intermolecular interactions for structurally similar domains in the PDB.
• Analysis of the NYN domain of ribonuclease N4BP1 revealed asymmetric distribution of protein-nucleotide interactions.
• Interactions were centered on the known nuclease active site of the NYN domain.

Conclusions:

• The enhanced DASH tool provides a powerful method for exploring protein structural similarity and associated intermolecular interactions.
• This extension aids in understanding protein function and active site characteristics by analyzing interaction patterns.
• The findings highlight the utility of DASH in uncovering biologically relevant interaction networks within the PDB.