Cargando…

Recognition of Functional Sites in Protein Structures()

Recognition of regions on the surface of one protein, that are similar to a binding site of another is crucial for the prediction of molecular interactions and for functional classifications. We first describe a novel method, SiteEngine, that assumes no sequence or fold similarities and is able to r...

Descripción completa

Detalles Bibliográficos
Autores principales: Shulman-Peleg, Alexandra, Nussinov, Ruth, Wolfson, Haim J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126412/
https://www.ncbi.nlm.nih.gov/pubmed/15147845
http://dx.doi.org/10.1016/j.jmb.2004.04.012
_version_ 1783516140364890112
author Shulman-Peleg, Alexandra
Nussinov, Ruth
Wolfson, Haim J.
author_facet Shulman-Peleg, Alexandra
Nussinov, Ruth
Wolfson, Haim J.
author_sort Shulman-Peleg, Alexandra
collection PubMed
description Recognition of regions on the surface of one protein, that are similar to a binding site of another is crucial for the prediction of molecular interactions and for functional classifications. We first describe a novel method, SiteEngine, that assumes no sequence or fold similarities and is able to recognize proteins that have similar binding sites and may perform similar functions. We achieve high efficiency and speed by introducing a low-resolution surface representation via chemically important surface points, by hashing triangles of physico-chemical properties and by application of hierarchical scoring schemes for a thorough exploration of global and local similarities. We proceed to rigorously apply this method to functional site recognition in three possible ways: first, we search a given functional site on a large set of complete protein structures. Second, a potential functional site on a protein of interest is compared with known binding sites, to recognize similar features. Third, a complete protein structure is searched for the presence of an a priori unknown functional site, similar to known sites. Our method is robust and efficient enough to allow computationally demanding applications such as the first and the third. From the biological standpoint, the first application may identify secondary binding sites of drugs that may lead to side-effects. The third application finds new potential sites on the protein that may provide targets for drug design. Each of the three applications may aid in assigning a function and in classification of binding patterns. We highlight the advantages and disadvantages of each type of search, provide examples of large-scale searches of the entire Protein Data Base and make functional predictions.
format Online
Article
Text
id pubmed-7126412
institution National Center for Biotechnology Information
language English
publishDate 2004
publisher Elsevier Ltd.
record_format MEDLINE/PubMed
spelling pubmed-71264122020-04-08 Recognition of Functional Sites in Protein Structures() Shulman-Peleg, Alexandra Nussinov, Ruth Wolfson, Haim J. J Mol Biol Article Recognition of regions on the surface of one protein, that are similar to a binding site of another is crucial for the prediction of molecular interactions and for functional classifications. We first describe a novel method, SiteEngine, that assumes no sequence or fold similarities and is able to recognize proteins that have similar binding sites and may perform similar functions. We achieve high efficiency and speed by introducing a low-resolution surface representation via chemically important surface points, by hashing triangles of physico-chemical properties and by application of hierarchical scoring schemes for a thorough exploration of global and local similarities. We proceed to rigorously apply this method to functional site recognition in three possible ways: first, we search a given functional site on a large set of complete protein structures. Second, a potential functional site on a protein of interest is compared with known binding sites, to recognize similar features. Third, a complete protein structure is searched for the presence of an a priori unknown functional site, similar to known sites. Our method is robust and efficient enough to allow computationally demanding applications such as the first and the third. From the biological standpoint, the first application may identify secondary binding sites of drugs that may lead to side-effects. The third application finds new potential sites on the protein that may provide targets for drug design. Each of the three applications may aid in assigning a function and in classification of binding patterns. We highlight the advantages and disadvantages of each type of search, provide examples of large-scale searches of the entire Protein Data Base and make functional predictions. Elsevier Ltd. 2004-06-04 2004-04-28 /pmc/articles/PMC7126412/ /pubmed/15147845 http://dx.doi.org/10.1016/j.jmb.2004.04.012 Text en Copyright © 2004 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Shulman-Peleg, Alexandra
Nussinov, Ruth
Wolfson, Haim J.
Recognition of Functional Sites in Protein Structures()
title Recognition of Functional Sites in Protein Structures()
title_full Recognition of Functional Sites in Protein Structures()
title_fullStr Recognition of Functional Sites in Protein Structures()
title_full_unstemmed Recognition of Functional Sites in Protein Structures()
title_short Recognition of Functional Sites in Protein Structures()
title_sort recognition of functional sites in protein structures()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126412/
https://www.ncbi.nlm.nih.gov/pubmed/15147845
http://dx.doi.org/10.1016/j.jmb.2004.04.012
work_keys_str_mv AT shulmanpelegalexandra recognitionoffunctionalsitesinproteinstructures
AT nussinovruth recognitionoffunctionalsitesinproteinstructures
AT wolfsonhaimj recognitionoffunctionalsitesinproteinstructures