Solvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design

Shiva Irani1, Seyed Mohammad Atyabi2, Houri Mivehchi3, Seyed Davar Siadat2, Mohammad Reza Aghasadeghi2, Ali Farhangi21Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran; 2Department of Pilot Biotechnology, Pasteur Institute of Iran, Tehran, Iran; 3Department of...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Irani S, Atyabi SM, Mivehchi H, Siadat SD, Aghasadeghi MR, Farhangi A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/718e3832dccf4a3b9354adc77c84be29
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:718e3832dccf4a3b9354adc77c84be29
record_format	dspace
spelling	oai:doaj.org-article:718e3832dccf4a3b9354adc77c84be292021-12-02T05:02:10ZSolvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design1176-91141178-2013https://doaj.org/article/718e3832dccf4a3b9354adc77c84be292011-09-01T00:00:00Zhttp://www.dovepress.com/solvent-effects-on-structural-and-thermochemical-properties-of-p53-tum-a8323https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Shiva Irani1, Seyed Mohammad Atyabi2, Houri Mivehchi3, Seyed Davar Siadat2, Mohammad Reza Aghasadeghi2, Ali Farhangi21Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran; 2Department of Pilot Biotechnology, Pasteur Institute of Iran, Tehran, Iran; 3Department of Novel Drug Delivery System, Iran Polymer and Petrochemical Institute, Tehran, IranAbstract: The p53 tumor-suppressor protein is a cellular phosphoprotein and a negative regulator of cell growth. Most p53 mutations occur in exons 5&ndash;8 within the DNA-binding domain. Therefore, p53 can potentially be targeted with novel drugs designed to bind to a mutation and restore its stability or wild-type conformation. For the current study, Hartree&ndash;Fock calculations were used to investigate the solvent-induced effects of five different solvent media (acetone, ethanol, methanol, dimethyl sulfoxide, and water) on the thermochemical parameters and relative energies, and on the multinuclear nuclear magnetic resonance shielding tensors of oxygen, nitrogen, and phosphorus nuclei, of GAT. To understand how the solvent affects the mutation region (the &ldquo;hot spot&rdquo;) of p53, the relative energies of GAT in selected solvent media were determined. Some biological evidence suggested the structural stabilities of hot spots of GAT have the optimum temperature and solvent type for mutation. All the authors&rsquo; findings are in accordance with common biological phenomena. Another important objective of this study was to compare the hydration Gibbs free energies of CUA and GAT in water using two different approaches where the solvent was treated as a continuum of the constant at different levels of Hartree&ndash;Fock theory. The Gibbs hydration energy values obtained in water with the polarized continuum model directly applied on the isolated CUA and GAT sequences were compared with those determined from the hydrated models with four, six, and eight water molecule clusters around the hot spots uracil and adenine. The clustered structures of water molecules around the hot spots of GAT (in DNA level) and CUA (in transcriptional level) were found to be energetically favored. The results of this study provide a reliable insight into the nature of mutation processes, which is of utmost importance for the study of biochemical structures, and provide a basis for drug design.Keywords: polarized continuum model (PCM), nuclear magnetic resonance (NMR), Hartree&ndash;Fock theoryIrani SAtyabi SMMivehchi HSiadat SDAghasadeghi MRFarhangi ADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2063-2069 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Irani S Atyabi SM Mivehchi H Siadat SD Aghasadeghi MR Farhangi A Solvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design
description	Shiva Irani1, Seyed Mohammad Atyabi2, Houri Mivehchi3, Seyed Davar Siadat2, Mohammad Reza Aghasadeghi2, Ali Farhangi21Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran; 2Department of Pilot Biotechnology, Pasteur Institute of Iran, Tehran, Iran; 3Department of Novel Drug Delivery System, Iran Polymer and Petrochemical Institute, Tehran, IranAbstract: The p53 tumor-suppressor protein is a cellular phosphoprotein and a negative regulator of cell growth. Most p53 mutations occur in exons 5&ndash;8 within the DNA-binding domain. Therefore, p53 can potentially be targeted with novel drugs designed to bind to a mutation and restore its stability or wild-type conformation. For the current study, Hartree&ndash;Fock calculations were used to investigate the solvent-induced effects of five different solvent media (acetone, ethanol, methanol, dimethyl sulfoxide, and water) on the thermochemical parameters and relative energies, and on the multinuclear nuclear magnetic resonance shielding tensors of oxygen, nitrogen, and phosphorus nuclei, of GAT. To understand how the solvent affects the mutation region (the &ldquo;hot spot&rdquo;) of p53, the relative energies of GAT in selected solvent media were determined. Some biological evidence suggested the structural stabilities of hot spots of GAT have the optimum temperature and solvent type for mutation. All the authors&rsquo; findings are in accordance with common biological phenomena. Another important objective of this study was to compare the hydration Gibbs free energies of CUA and GAT in water using two different approaches where the solvent was treated as a continuum of the constant at different levels of Hartree&ndash;Fock theory. The Gibbs hydration energy values obtained in water with the polarized continuum model directly applied on the isolated CUA and GAT sequences were compared with those determined from the hydrated models with four, six, and eight water molecule clusters around the hot spots uracil and adenine. The clustered structures of water molecules around the hot spots of GAT (in DNA level) and CUA (in transcriptional level) were found to be energetically favored. The results of this study provide a reliable insight into the nature of mutation processes, which is of utmost importance for the study of biochemical structures, and provide a basis for drug design.Keywords: polarized continuum model (PCM), nuclear magnetic resonance (NMR), Hartree&ndash;Fock theory
format	article
author	Irani S Atyabi SM Mivehchi H Siadat SD Aghasadeghi MR Farhangi A
author_facet	Irani S Atyabi SM Mivehchi H Siadat SD Aghasadeghi MR Farhangi A
author_sort	Irani S
title	Solvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design
title_short	Solvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design
title_full	Solvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design
title_fullStr	Solvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design
title_full_unstemmed	Solvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design
title_sort	solvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/718e3832dccf4a3b9354adc77c84be29
work_keys_str_mv	AT iranis solventeffectsonstructuralandthermochemicalpropertiesofp53tumorsuppressorgeneamolecularmodelingapproachindrugdesign AT atyabism solventeffectsonstructuralandthermochemicalpropertiesofp53tumorsuppressorgeneamolecularmodelingapproachindrugdesign AT mivehchih solventeffectsonstructuralandthermochemicalpropertiesofp53tumorsuppressorgeneamolecularmodelingapproachindrugdesign AT siadatsd solventeffectsonstructuralandthermochemicalpropertiesofp53tumorsuppressorgeneamolecularmodelingapproachindrugdesign AT aghasadeghimr solventeffectsonstructuralandthermochemicalpropertiesofp53tumorsuppressorgeneamolecularmodelingapproachindrugdesign AT farhangia solventeffectsonstructuralandthermochemicalpropertiesofp53tumorsuppressorgeneamolecularmodelingapproachindrugdesign
_version_	1718400771768188928

Solvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design

Ejemplares similares