Open-access Mustguseal platform for bioinformatic analysis in computational enzymology

Comparative analysis of homologous proteins in a functionally diverse superfamily is a valuable tool at studying structure-­function relationship, but represents a methodological challenge. We have developed an open-­access platform uniting original on-line methods to study the structure-­function relationship in proteins, to select the most promising hot-­spots for implementation of novel functions, improvement of stability and evolvability of useful proteins/enzymes, and to design of their selective modulators.

 

 

 

Mustguseal web-­server can automatically collect and align thousands of homologous protein sequences and structures [Bioinformatics, 2018, DOI:10.1093/bioinformatics/btx831]

Five sister web-­methods are available for subsequent bioinformatic analysis of the collected data:

  • Zebra web-server to identify and prioritize conserved and specific positions in a functionally diverse superfamily and to select hot-spots for rational design of the query protein [Nucleic Acids Res., 2020, DOI:10.1093/nar/gkaa276];
  • Zebra3D tool for bioinformatic analysis of 3D-determinants of functional diversity and function-related conformational plasticity in protein superfamilies using machine learning [Comput. Struct. Biotechnol. J., 2021, DOI:10.1016/j.csbj.2021.02.005];
  • the pocketZebra web-server to identify and rank binding sites in proteins by their functional significance and to select particular positions in the structure important for selective binding of substrates/inhibitors/effectors [Nucleic Acids Res., 2014, DOI:10.1093/nar/gku448];
  • the visualCMAT web-server to select and interpret correlated mutations/co-­evolving residues in protein structures [J Bioinform Comput Biol., 2018, DOI:10.1142/S021972001840005X];
  • Yosshi web­-server to classify and study disulfide bonds in protein families as well as to select hot­-spots for disulfide engineering [Nucleic Acids Res., 2019, DOI:10.1093/nar/gkz385].

 

Integration of these bioinformatic web-tools provides an out-­of­-the­box easy­-to-­use solution, first of its kind, to systematically analyze all the available sequence and structural data related to a protein superfamily, thus promoting the value of bioinformatics for protein engineering and drug discovery.

Practical guide: Suplatov D., Sharapova Y., Švedas V. (2021) Mustguseal and Sister Web-Methods: A Practical Guide to Bioinformatic Analysis of Protein Superfamilies. In: Katoh K. (eds) Multiple Sequence Alignment. Methods in Molecular Biology, vol 2231. Humana, New York, NY. DOI: 10.1007/978-1-0716-1036-7_12.

A brief overview of the Mustguseal platform:

 

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This work is being funded by the Russian Foundation for Basic Research [#18-­29-­13060] and carried out using the HPC computing resources at the Lomonosov Moscow State University supported by the project RFMEFI62117X0011.