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Match_Motif: A rapid computational tool to assist in protein–protein interaction design
In order to generate protein assemblies with a desired function, the rational design of protein–protein binding interfaces is of significant interest. Approaches based on random mutagenesis or directed evolution may involve complex experimental selection procedures. Also, molecular modeling approach...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740833/ https://www.ncbi.nlm.nih.gov/pubmed/34648221 http://dx.doi.org/10.1002/pro.4208 |
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author | Zacharias, Martin |
author_facet | Zacharias, Martin |
author_sort | Zacharias, Martin |
collection | PubMed |
description | In order to generate protein assemblies with a desired function, the rational design of protein–protein binding interfaces is of significant interest. Approaches based on random mutagenesis or directed evolution may involve complex experimental selection procedures. Also, molecular modeling approaches to design entirely new proteins and interactions with partner molecules can involve large computational efforts and screening steps. In order to simplify at least the initial effort for designing a putative binding interface between two proteins the Match_Motif approach has been developed. It employs the large collection of known protein–protein complex structures to suggest interface modifications that may lead to improved binding for a desired input interaction geometry. The approach extracts interaction motifs based on the backbone structure of short (four residues) segments and the relative arrangement with respect to short segments on the partner protein. The interaction geometry is used to search through a database of such motifs in known stable bound complexes. All matches are rapidly identified (within a few seconds) and collected and can be used to guide changes in the interface that may lead to improved binding. In the output, an alternative interface structure is also proposed based on the frequency of occurrence of side chains at a given interface position in all matches and based on sterical considerations. Applications of the procedure to known complex structures and alternative arrangements are presented and discussed. The program, data files, and example applications can be downloaded from https://www.groups.ph.tum.de/t38/downloads/. |
format | Online Article Text |
id | pubmed-8740833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87408332022-01-12 Match_Motif: A rapid computational tool to assist in protein–protein interaction design Zacharias, Martin Protein Sci Tools for Protein Science In order to generate protein assemblies with a desired function, the rational design of protein–protein binding interfaces is of significant interest. Approaches based on random mutagenesis or directed evolution may involve complex experimental selection procedures. Also, molecular modeling approaches to design entirely new proteins and interactions with partner molecules can involve large computational efforts and screening steps. In order to simplify at least the initial effort for designing a putative binding interface between two proteins the Match_Motif approach has been developed. It employs the large collection of known protein–protein complex structures to suggest interface modifications that may lead to improved binding for a desired input interaction geometry. The approach extracts interaction motifs based on the backbone structure of short (four residues) segments and the relative arrangement with respect to short segments on the partner protein. The interaction geometry is used to search through a database of such motifs in known stable bound complexes. All matches are rapidly identified (within a few seconds) and collected and can be used to guide changes in the interface that may lead to improved binding. In the output, an alternative interface structure is also proposed based on the frequency of occurrence of side chains at a given interface position in all matches and based on sterical considerations. Applications of the procedure to known complex structures and alternative arrangements are presented and discussed. The program, data files, and example applications can be downloaded from https://www.groups.ph.tum.de/t38/downloads/. John Wiley & Sons, Inc. 2021-10-26 2022-01 /pmc/articles/PMC8740833/ /pubmed/34648221 http://dx.doi.org/10.1002/pro.4208 Text en © 2021 The Author. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Tools for Protein Science Zacharias, Martin Match_Motif: A rapid computational tool to assist in protein–protein interaction design |
title | Match_Motif: A rapid computational tool to assist in protein–protein interaction design |
title_full | Match_Motif: A rapid computational tool to assist in protein–protein interaction design |
title_fullStr | Match_Motif: A rapid computational tool to assist in protein–protein interaction design |
title_full_unstemmed | Match_Motif: A rapid computational tool to assist in protein–protein interaction design |
title_short | Match_Motif: A rapid computational tool to assist in protein–protein interaction design |
title_sort | match_motif: a rapid computational tool to assist in protein–protein interaction design |
topic | Tools for Protein Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740833/ https://www.ncbi.nlm.nih.gov/pubmed/34648221 http://dx.doi.org/10.1002/pro.4208 |
work_keys_str_mv | AT zachariasmartin matchmotifarapidcomputationaltooltoassistinproteinproteininteractiondesign |