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.
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.