Building multiple sequence alignments with a flavor of HSSP alignments

Area of Science:

• Bioinformatics
• Computational Biology
• Structural Bioinformatics

Background:

• Homology-derived secondary structure of proteins (HSSP) aligns protein sequences with 3D structures from the Protein Data Bank (PDB).
• Existing tools like STING and (Java)Protein Dossier use HSSP for residue conservation analysis but are limited to PDB-deposited structures.
• Analysis of modeled or non-PDB structures requires new alignment methods.

Purpose of the Study:

• To introduce a novel method (myMSAr) and database (SH2QS) for generating protein sequence alignments.
• To enable residue conservation measurement for any query sequence, irrespective of PDB structure deposition.
• To compare the conservation analysis derived from HSSP and the new SH2QS method.

Main Methods:

• Development of myMSAr, a method for building HSSP-like alignments.
• Creation of the SH2QS database, containing sequences homologous to query sequences.
• Comparative analysis of residue conservation measurements between HSSP and SH2QS alignments.

Main Results:

• The study presents SH2QS as a viable alternative for residue conservation analysis.
• Case studies demonstrate the equivalence of HSSP and SH2QS for PDB-deposited structures.
• SH2QS successfully provides conservation data for a computer-modeled protein structure absent in HSSP.

Conclusions:

• The SH2QS database and myMSAr method effectively measure protein residue conservation.
• This approach extends conservation analysis to proteins without experimentally determined or PDB-deposited structures.
• SH2QS facilitates broader structural bioinformatics research by including modeled proteins.