Publication Details

HotSpot Wizard 3.0: Web Server for Automated Design of Mutations and Smart Libraries based on Sequence Input Information.

SUMBALOVÁ, L.; ŠTOURAČ, J.; MARTÍNEK, T.; BEDNÁŘ, D.; DAMBORSKÝ, J. HotSpot Wizard 3.0: Web Server for Automated Design of Mutations and Smart Libraries based on Sequence Input Information. Nucleic Acids Research, 2018, vol. 46, no. 1, p. 356-362. ISSN: 1362-4962.
Czech title
HotSpot Wizard 3.0: Webový server pro automatický návrh mutací a chytrých knihoven na základě sekvenčních informací
Type
journal article
Language
English
Authors
Sumbalová Lenka, Ing.
Štourač Jan (FIT)
Martínek Tomáš, doc. Ing., Ph.D. (DCSY)
Bednář David (FIT)
Damborský Jiří, prof. Mgr., Dr. (UMEL)
URL
Keywords

Hot spots, proteins, homology modelling, stability.

Abstract

HotSpot Wizard is a web server used for the automated identification of hotspots in semi-rational protein design to give improved protein stability, catalytic activity, substrate specificity and enantioselectivity. Since there are three orders of magnitude fewer protein structures than sequences in bioinformatic databases, the major limitation to the usability of previous versions was the requirement for the protein structure to be a compulsory input for the calculation. HotSpot Wizard 3.0 now accepts the protein sequence as input data. The protein structure for the query sequence is obtained either from eight repositories of homology models or is modeled using Modeller and I-Tasser. The quality of the models is then evaluated using three quality assessment tools-WHAT_CHECK, PROCHECK and MolProbity. During follow-up analyses, the system automatically warns the users whenever they attempt to redesign poorly predicted parts of their homology models. The second main limitation of HotSpot Wizard's predictions is that it identifies suitable positions for mutagenesis, but does not provide any reliable advice on particular substitutions. A new module for the estimation of thermodynamic stabilities using the Rosetta and FoldX suites has been introduced which prevents destabilizing mutations among pre-selected variants entering experimental testing. HotSpot Wizard is freely available at http://loschmidt.chemi.muni.cz/hotspotwizard.

Published
2018
Pages
356–362
Journal
Nucleic Acids Research, vol. 46, no. 1, ISSN 1362-4962
DOI
10.1093/nar/gky417
UT WoS
000438374100057
EID Scopus
2-s2.0-85050851556
BibTeX 
@article{BUT155055,
  author="Lenka {Sumbalová} and Jan {Štourač} and Tomáš {Martínek} and David {Bednář} and Jiří {Damborský}",
  title="HotSpot Wizard 3.0: Web Server for Automated Design of Mutations and Smart Libraries based on Sequence Input Information.",
  journal="Nucleic Acids Research",
  year="2018",
  volume="46",
  number="1",
  pages="356--362",
  doi="10.1093/nar/gky417",
  issn="1362-4962",
  url="https://doi.org/10.1093/nar/gky417"
}
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