Publication detail

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.

Original Title

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

Type

journal article in Web of Science

Language

English

Original 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.

Keywords

Hot spots, proteins, homology modelling, stability.

Authors

SUMBALOVÁ, L.; ŠTOURAČ, J.; MARTÍNEK, T.; BEDNÁŘ, D.; DAMBORSKÝ, J.

Released

17. 5. 2018

ISBN

1362-4962

Periodical

Nucleic Acids Research

Year of study

46

Number

1

State

United Kingdom of Great Britain and Northern Ireland

Pages from

356

Pages to

362

Pages count

7

URL

https://doi.org/10.1093/nar/gky417

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"
}