BioGPS descriptors for rational engineering of enzyme promiscuity and structure based bioinformatic analysis

PLoS One. 2014 Oct 29;9(10):e109354. doi: 10.1371/journal.pone.0109354. eCollection 2014.

Abstract

A new bioinformatic methodology was developed founded on the Unsupervised Pattern Cognition Analysis of GRID-based BioGPS descriptors (Global Positioning System in Biological Space). The procedure relies entirely on three-dimensional structure analysis of enzymes and does not stem from sequence or structure alignment. The BioGPS descriptors account for chemical, geometrical and physical-chemical features of enzymes and are able to describe comprehensively the active site of enzymes in terms of "pre-organized environment" able to stabilize the transition state of a given reaction. The efficiency of this new bioinformatic strategy was demonstrated by the consistent clustering of four different Ser hydrolases classes, which are characterized by the same active site organization but able to catalyze different reactions. The method was validated by considering, as a case study, the engineering of amidase activity into the scaffold of a lipase. The BioGPS tool predicted correctly the properties of lipase variants, as demonstrated by the projection of mutants inside the BioGPS "roadmap".

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / chemistry*
  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism
  • Bioengineering
  • Catalytic Domain
  • Computational Biology / methods*
  • Lipase / chemistry*
  • Lipase / genetics
  • Lipase / metabolism
  • Models, Molecular
  • Protein Conformation
  • Reproducibility of Results

Substances

  • Lipase
  • Amidohydrolases
  • amidase

Grants and funding

This work has received funding from the European Community’s Seventh Framework Programme under the FP7-KBBE-2008-2B grant agreement n° 227279. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Moreover: MB is an employee of Molecular Discovery Ltd. Molecular Discovery Ltd provided support in the form of salary for author MB but Molecular Discovery Ltd. did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.