In silico prediction of mutant HIV-1 proteases cleaving a target sequence.
HIV-1 protease represents an appealing system for directed enzyme re-design, since it has various different endogenous targets, a relatively simple structure and it is well studied. Recently Chaudhury and Gray (Structure (2009) 17: 1636-1648) published a computational algorithm to discern the specif...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095833&type=printable |
| _version_ | 1826587260172107776 |
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| author | Jan H Jensen Martin Willemoës Jakob R Winther Luca De Vico |
| author_facet | Jan H Jensen Martin Willemoës Jakob R Winther Luca De Vico |
| author_sort | Jan H Jensen |
| collection | DOAJ |
| description | HIV-1 protease represents an appealing system for directed enzyme re-design, since it has various different endogenous targets, a relatively simple structure and it is well studied. Recently Chaudhury and Gray (Structure (2009) 17: 1636-1648) published a computational algorithm to discern the specificity determining residues of HIV-1 protease. In this paper we present two computational tools aimed at re-designing HIV-1 protease, derived from the algorithm of Chaudhuri and Gray. First, we present an energy-only based methodology to discriminate cleavable and non cleavable peptides for HIV-1 proteases, both wild type and mutant. Secondly, we show an algorithm we developed to predict mutant HIV-1 proteases capable of cleaving a new target substrate peptide, different from the natural targets of HIV-1 protease. The obtained in silico mutant enzymes were analyzed in terms of cleavability and specificity towards the target peptide using the energy-only methodology. We found two mutant proteases as best candidates for specificity and cleavability towards the target sequence. |
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| id | doaj.art-e5e72c6fe5074f11a685360c2d3d5bb1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T16:22:36Z |
| publishDate | 2014-01-01 |
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| spelling | doaj.art-e5e72c6fe5074f11a685360c2d3d5bb12025-02-22T05:32:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9583310.1371/journal.pone.0095833In silico prediction of mutant HIV-1 proteases cleaving a target sequence.Jan H JensenMartin WillemoësJakob R WintherLuca De VicoHIV-1 protease represents an appealing system for directed enzyme re-design, since it has various different endogenous targets, a relatively simple structure and it is well studied. Recently Chaudhury and Gray (Structure (2009) 17: 1636-1648) published a computational algorithm to discern the specificity determining residues of HIV-1 protease. In this paper we present two computational tools aimed at re-designing HIV-1 protease, derived from the algorithm of Chaudhuri and Gray. First, we present an energy-only based methodology to discriminate cleavable and non cleavable peptides for HIV-1 proteases, both wild type and mutant. Secondly, we show an algorithm we developed to predict mutant HIV-1 proteases capable of cleaving a new target substrate peptide, different from the natural targets of HIV-1 protease. The obtained in silico mutant enzymes were analyzed in terms of cleavability and specificity towards the target peptide using the energy-only methodology. We found two mutant proteases as best candidates for specificity and cleavability towards the target sequence.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095833&type=printable |
| spellingShingle | Jan H Jensen Martin Willemoës Jakob R Winther Luca De Vico In silico prediction of mutant HIV-1 proteases cleaving a target sequence. PLoS ONE |
| title | In silico prediction of mutant HIV-1 proteases cleaving a target sequence. |
| title_full | In silico prediction of mutant HIV-1 proteases cleaving a target sequence. |
| title_fullStr | In silico prediction of mutant HIV-1 proteases cleaving a target sequence. |
| title_full_unstemmed | In silico prediction of mutant HIV-1 proteases cleaving a target sequence. |
| title_short | In silico prediction of mutant HIV-1 proteases cleaving a target sequence. |
| title_sort | in silico prediction of mutant hiv 1 proteases cleaving a target sequence |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0095833&type=printable |
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