Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.

Protein denaturation plays a crucial role in cellular processes. In this study, denaturation of HIV-1 Protease (PR) was investigated by all-atom MD simulations in explicit solvent. The PR dimer and monomer were simulated separately in 9 M acetic acid (9 M AcOH) solution and water to study the denatu...

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Autores principales:	Aditi Narendra Borkar, Manoj Kumar Rout, Ramakrishna V Hosur
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/442e571f22174c5eb89ecf76ac235ca3
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spelling	oai:doaj.org-article:442e571f22174c5eb89ecf76ac235ca32021-11-18T06:51:03ZVisualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.1932-620310.1371/journal.pone.0019830https://doaj.org/article/442e571f22174c5eb89ecf76ac235ca32011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21738569/?tool=EBIhttps://doaj.org/toc/1932-6203Protein denaturation plays a crucial role in cellular processes. In this study, denaturation of HIV-1 Protease (PR) was investigated by all-atom MD simulations in explicit solvent. The PR dimer and monomer were simulated separately in 9 M acetic acid (9 M AcOH) solution and water to study the denaturation process of PR in acetic acid environment. Direct visualization of the denaturation dynamics that is readily available from such simulations has been presented. Our simulations in 9 M AcOH reveal that the PR denaturation begins by separation of dimer into intact monomers and it is only after this separation that the monomer units start denaturing. The denaturation of the monomers is flagged off by the loss of crucial interactions between the α-helix at C-terminal and surrounding β-strands. This causes the structure to transit from the equilibrium dynamics to random non-equilibrating dynamics. Residence time calculations indicate that denaturation occurs via direct interaction of the acetic acid molecules with certain regions of the protein in 9 M AcOH. All these observations have helped to decipher a picture of the early events in acetic acid denaturation of PR and have illustrated that the α-helix and the β-sheet at the C-terminus of a native and functional PR dimer should maintain both the stability and the function of the enzyme and thus present newer targets for blocking PR function.Aditi Narendra BorkarAditi Narendra BorkarManoj Kumar RoutRamakrishna V HosurPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 6, p e19830 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aditi Narendra Borkar Aditi Narendra Borkar Manoj Kumar Rout Ramakrishna V Hosur Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.
description	Protein denaturation plays a crucial role in cellular processes. In this study, denaturation of HIV-1 Protease (PR) was investigated by all-atom MD simulations in explicit solvent. The PR dimer and monomer were simulated separately in 9 M acetic acid (9 M AcOH) solution and water to study the denaturation process of PR in acetic acid environment. Direct visualization of the denaturation dynamics that is readily available from such simulations has been presented. Our simulations in 9 M AcOH reveal that the PR denaturation begins by separation of dimer into intact monomers and it is only after this separation that the monomer units start denaturing. The denaturation of the monomers is flagged off by the loss of crucial interactions between the α-helix at C-terminal and surrounding β-strands. This causes the structure to transit from the equilibrium dynamics to random non-equilibrating dynamics. Residence time calculations indicate that denaturation occurs via direct interaction of the acetic acid molecules with certain regions of the protein in 9 M AcOH. All these observations have helped to decipher a picture of the early events in acetic acid denaturation of PR and have illustrated that the α-helix and the β-sheet at the C-terminus of a native and functional PR dimer should maintain both the stability and the function of the enzyme and thus present newer targets for blocking PR function.
format	article
author	Aditi Narendra Borkar Aditi Narendra Borkar Manoj Kumar Rout Ramakrishna V Hosur
author_facet	Aditi Narendra Borkar Aditi Narendra Borkar Manoj Kumar Rout Ramakrishna V Hosur
author_sort	Aditi Narendra Borkar
title	Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.
title_short	Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.
title_full	Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.
title_fullStr	Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.
title_full_unstemmed	Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.
title_sort	visualization of early events in acetic acid denaturation of hiv-1 protease: a molecular dynamics study.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/442e571f22174c5eb89ecf76ac235ca3
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Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.

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