=Paper=
{{Paper
|id=Vol-1482/537
|storemode=property
|title=High-performance computing in bioinformatic analysis of protein superfamilies to design enzymes with new properties
|pdfUrl=https://ceur-ws.org/Vol-1482/537.pdf
|volume=Vol-1482
}}
==High-performance computing in bioinformatic analysis of protein superfamilies to design enzymes with new properties==
<pdf width="1500px">https://ceur-ws.org/Vol-1482/537.pdf</pdf>
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      Суперкомпьютерные дни в России 2015 // Russian Supercomputing Days 2015 // RussianSCDays.org



High-performance computing in bioinformatic analysis of protein
     superfamilies to design enzymes with new properties*
           D. Suplatov1, N. Popova2, K. Kopylov3, M. Shegai2, V. Voevodin4, V. Švedas1
    Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics and
    Belozersky Institute of Physicochemical Biology1, Faculty of Computational Mathematics
            and Cybernetics 2, Faculty of Chemistry 3, Research Computing Center 4

     Growing capacity of bioinformatic databases provides new opportunities to study structure-
function relationship in large protein superfamilies and greatly increases the demand for high perfor-
mance computing. However, the general-purpose parallel computing clusters do not provide optimal
accommodation to bioinformatic applications which are usually written using openMP rather than
MPI, Java or even Perl and Python. Distributed computing platforms are available as an inexpensive
alternative but they lack the power of a dedicated computing cluster. Based on the Lomonosov Mos-
cow State University supercomputer complex we are developing a platform which implements compu-
tational methods of bioinformatic analysis, molecular modeling and computational chemistry to study
the structure-function relationship in large enzyme superfamilies and produce novel biocatalysts with
improved properties. Co-design of cluster’s hardware and software according to demands of computa-
tional biology will provide a solution for large-scale tasks of biocatalysis.
     Homologous enzymes have evolved from a common ancestor to retain a general function but di-
verged in more specific features and can be divided into subfamilies with different functional proper-
ties such as catalytic activity, substrate specificity, enantioselectivity, stability, etc. Analysis of se-
quence and structural information in protein superfamilies is a promising trend in order to rationalize
enzyme engineering and move away from unguided evolutionary stochastic approaches and empirical
design [1]. We have recently developed a new method of bioinformatic analysis to identify function-
related variable residues in protein structures that are responsible for functional divergence within su-
perfamilies of homologous enzymes [2]. The developed methodology has been applied to study struc-
ture-functional relationship in various enzyme superfamilies: α/β-hydrolases, Ntn-hydrolases, penicil-
lin-binding proteins, etc. Systematic bioinformatic analysis of genomic and structural information cor-
responding to each selected superfamily of enzymes has been carried out to identify functionally im-
portant amino acid residues as hotspots for enzyme engineering. It has been shown that bioinformatic
analysis can be effectively used to design enzyme mutants with improved catalytic properties and to
predict functional properties of enzymes [3, 4]. There is a need to implement these computationally
demanding algorithms into the common laboratory practice to study the structure-function relationship
in proteins and develop novel protein engineering strategies.

References
1. Suplatov D., Voevodin V., Švedas V. Robust enzyme design: Bioinformatic tools for improved
   protein stability //Biotechnol. J. – 2015. – Vol. 10. – No. 3. – P. 344-355.
2. Suplatov D., Kirilin E., Arbatsky M., Takhaveev V., Švedas V. pocketZebra: a web-server for au-
   tomated selection and classification of subfamily-specific binding sites by bioinformatic analysis
   of diverse protein families //Nucl. Acids Res. – 2014. – Vol. 42. – No. W1 – P. W344-W349.
3. Suplatov D., Besenmatter W., Švedas V., Svendsen A. Bioinformatic analysis of alpha/beta-
   hydrolase fold enzymes reveals subfamily-specific positions responsible for discrimination of
   amidase and lipase activities //Protein Eng. Des. Sel. – 2012. – Vol. 25. – No. 11 – P. 689-697.
4. Suplatov D., Panin N., Kirilin E., Shcherbakova T., Kudryavtsev P., Švedas V. Computational
   Design of a pH Stable Enzyme: Understanding Molecular Mechanism of Penicillin Acylase's Ad-
   aptation to Alkaline Conditions //PloS one. – 2014. – Vol. 9. – No. 6. – P. e100643.

*
    This work was supported by Russian Foundation for Basic Research grant No. 14-07-00437


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