An integrated platform for automatic design and screening of virtual mutants based on 3D-QSAR analysis
tAn innovative application of 3D-QSAR methodology to the rational design of enzymes is here reported.The introduction of amidase activity inside the scaffold of lipase B from Candida antarctica (CaLB) wasstudied and 3D-QSAR models were constructed to correlate the structures of a set of CaLB mutants...
Published in: | Journal of Molecular Catalysis B: Enzymatic |
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ftunitriestiris:oai:arts.units.it:11368/2744899 2023-05-15T14:13:51+02:00 An integrated platform for automatic design and screening of virtual mutants based on 3D-QSAR analysis FERRARIO, VALERIO EBERT, CYNTHIA GARDOSSI, Lucia Svendsen A. Besenmatter W. Ferrario, Valerio Ebert, Cynthia Svendsen, A. Besenmatter, W. Gardossi, Lucia 2014 STAMPA http://hdl.handle.net/11368/2744899 https://doi.org/10.1016/j.molcatb.2013.12.004 eng eng info:eu-repo/semantics/altIdentifier/wos/WOS:000332142400002 volume:101, 2014 firstpage:7 lastpage:15 numberofpages:9 journal:JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC http://hdl.handle.net/11368/2744899 doi:10.1016/j.molcatb.2013.12.004 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84892757242 computational chemistry enzyme engineering 3DQSAR biocatalysi lipase amidases info:eu-repo/semantics/article 2014 ftunitriestiris https://doi.org/10.1016/j.molcatb.2013.12.004 2023-04-09T06:11:38Z tAn innovative application of 3D-QSAR methodology to the rational design of enzymes is here reported.The introduction of amidase activity inside the scaffold of lipase B from Candida antarctica (CaLB) wasstudied and 3D-QSAR models were constructed to correlate the structures of a set of CaLB mutants withtheir experimentally measured activities. Properties, like hydrophilicity, hydrophobicity and hydrogenbonding capability of the enzyme active site were computed by means of the GRID method and theoutput was used as molecular descriptors. Correlations with experimental behavior of the catalysts werecalculated by means of partial least square regression (PLS). The analysis of the QSAR model fully exploitsfundamental knowledge while avoiding conceptual biases. Rationales for driving enzyme engineeringare disclosed and a priori evaluation of new virtual candidate mutants becomes feasible. On that respect,the whole procedure for production of virtual mutants and scoring of their activity was automated withina workflow constructed by means of the modeFRONTIER package. The method allows for the automatedconstruction and scoring of each mutant in 2 h on a normal workstation. Article in Journal/Newspaper Antarc* Antarctica Università degli studi di Trieste: ArTS (Archivio della ricerca di Trieste) Journal of Molecular Catalysis B: Enzymatic 101 7 15 |
institution |
Open Polar |
collection |
Università degli studi di Trieste: ArTS (Archivio della ricerca di Trieste) |
op_collection_id |
ftunitriestiris |
language |
English |
topic |
computational chemistry enzyme engineering 3DQSAR biocatalysi lipase amidases |
spellingShingle |
computational chemistry enzyme engineering 3DQSAR biocatalysi lipase amidases FERRARIO, VALERIO EBERT, CYNTHIA GARDOSSI, Lucia Svendsen A. Besenmatter W. An integrated platform for automatic design and screening of virtual mutants based on 3D-QSAR analysis |
topic_facet |
computational chemistry enzyme engineering 3DQSAR biocatalysi lipase amidases |
description |
tAn innovative application of 3D-QSAR methodology to the rational design of enzymes is here reported.The introduction of amidase activity inside the scaffold of lipase B from Candida antarctica (CaLB) wasstudied and 3D-QSAR models were constructed to correlate the structures of a set of CaLB mutants withtheir experimentally measured activities. Properties, like hydrophilicity, hydrophobicity and hydrogenbonding capability of the enzyme active site were computed by means of the GRID method and theoutput was used as molecular descriptors. Correlations with experimental behavior of the catalysts werecalculated by means of partial least square regression (PLS). The analysis of the QSAR model fully exploitsfundamental knowledge while avoiding conceptual biases. Rationales for driving enzyme engineeringare disclosed and a priori evaluation of new virtual candidate mutants becomes feasible. On that respect,the whole procedure for production of virtual mutants and scoring of their activity was automated withina workflow constructed by means of the modeFRONTIER package. The method allows for the automatedconstruction and scoring of each mutant in 2 h on a normal workstation. |
author2 |
Ferrario, Valerio Ebert, Cynthia Svendsen, A. Besenmatter, W. Gardossi, Lucia |
format |
Article in Journal/Newspaper |
author |
FERRARIO, VALERIO EBERT, CYNTHIA GARDOSSI, Lucia Svendsen A. Besenmatter W. |
author_facet |
FERRARIO, VALERIO EBERT, CYNTHIA GARDOSSI, Lucia Svendsen A. Besenmatter W. |
author_sort |
FERRARIO, VALERIO |
title |
An integrated platform for automatic design and screening of virtual mutants based on 3D-QSAR analysis |
title_short |
An integrated platform for automatic design and screening of virtual mutants based on 3D-QSAR analysis |
title_full |
An integrated platform for automatic design and screening of virtual mutants based on 3D-QSAR analysis |
title_fullStr |
An integrated platform for automatic design and screening of virtual mutants based on 3D-QSAR analysis |
title_full_unstemmed |
An integrated platform for automatic design and screening of virtual mutants based on 3D-QSAR analysis |
title_sort |
integrated platform for automatic design and screening of virtual mutants based on 3d-qsar analysis |
publishDate |
2014 |
url |
http://hdl.handle.net/11368/2744899 https://doi.org/10.1016/j.molcatb.2013.12.004 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
info:eu-repo/semantics/altIdentifier/wos/WOS:000332142400002 volume:101, 2014 firstpage:7 lastpage:15 numberofpages:9 journal:JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC http://hdl.handle.net/11368/2744899 doi:10.1016/j.molcatb.2013.12.004 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84892757242 |
op_doi |
https://doi.org/10.1016/j.molcatb.2013.12.004 |
container_title |
Journal of Molecular Catalysis B: Enzymatic |
container_volume |
101 |
container_start_page |
7 |
op_container_end_page |
15 |
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1766286388498530304 |