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Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains

[Image: see text] With the aim of investigating the relationship between the fast fluctuations of proteins and their allosteric behavior, we perform molecular dynamics simulations of two model PDZ domains with differential allosteric responses. We focus on protein dynamics in the THz regime (0.1–3 T...

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Autores principales: Conti Nibali, Valeria, Morra, Giulia, Havenith, Martina, Colombo, Giorgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421520/
https://www.ncbi.nlm.nih.gov/pubmed/28991478
http://dx.doi.org/10.1021/acs.jpcb.7b06590
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author Conti Nibali, Valeria
Morra, Giulia
Havenith, Martina
Colombo, Giorgio
author_facet Conti Nibali, Valeria
Morra, Giulia
Havenith, Martina
Colombo, Giorgio
author_sort Conti Nibali, Valeria
collection PubMed
description [Image: see text] With the aim of investigating the relationship between the fast fluctuations of proteins and their allosteric behavior, we perform molecular dynamics simulations of two model PDZ domains with differential allosteric responses. We focus on protein dynamics in the THz regime (0.1–3 THz) as opposed to lower frequencies. By characterizing the dynamic modulation of the protein backbone induced by ligand binding in terms of single residue and pairwise distance fluctuations, we identify a response nucleus modulated by the ligand that is visible only at THz frequencies. The residues of this nucleus undergo a significant stiffening and an increase in mutual coordination upon binding. Additionally, we find that the dynamic modulation is significantly more intense for the side chains, where it is also redistributed to distal regions not immediately in contact with the ligand allowing us to better define the response nucleus at THz frequencies. The overlap between the known allosterically responding residues of the investigated PDZ domains and the modulated region highlighted here suggests that fast THz dynamics could play a role in allosteric mechanisms.
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spelling pubmed-64215202019-03-19 Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains Conti Nibali, Valeria Morra, Giulia Havenith, Martina Colombo, Giorgio J Phys Chem B [Image: see text] With the aim of investigating the relationship between the fast fluctuations of proteins and their allosteric behavior, we perform molecular dynamics simulations of two model PDZ domains with differential allosteric responses. We focus on protein dynamics in the THz regime (0.1–3 THz) as opposed to lower frequencies. By characterizing the dynamic modulation of the protein backbone induced by ligand binding in terms of single residue and pairwise distance fluctuations, we identify a response nucleus modulated by the ligand that is visible only at THz frequencies. The residues of this nucleus undergo a significant stiffening and an increase in mutual coordination upon binding. Additionally, we find that the dynamic modulation is significantly more intense for the side chains, where it is also redistributed to distal regions not immediately in contact with the ligand allowing us to better define the response nucleus at THz frequencies. The overlap between the known allosterically responding residues of the investigated PDZ domains and the modulated region highlighted here suggests that fast THz dynamics could play a role in allosteric mechanisms. American Chemical Society 2017-10-09 2017-11-09 /pmc/articles/PMC6421520/ /pubmed/28991478 http://dx.doi.org/10.1021/acs.jpcb.7b06590 Text en Copyright © 2017 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Conti Nibali, Valeria
Morra, Giulia
Havenith, Martina
Colombo, Giorgio
Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains
title Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains
title_full Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains
title_fullStr Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains
title_full_unstemmed Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains
title_short Role of Terahertz (THz) Fluctuations in the Allosteric Properties of the PDZ Domains
title_sort role of terahertz (thz) fluctuations in the allosteric properties of the pdz domains
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421520/
https://www.ncbi.nlm.nih.gov/pubmed/28991478
http://dx.doi.org/10.1021/acs.jpcb.7b06590
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