Cargando…

Atomic Resolution Homology Models and Molecular Dynamics Simulations of Plasmodium falciparum Tubulins

[Image: see text] Microtubules are tubulin polymers present in the eukaryotic cytoskeleton essential for structural stability and cell division that are also roadways for intracellular transport of vesicles and organelles. In the human malaria parasite Plasmodium falciparum, apart from providing str...

Descripción completa

Detalles Bibliográficos
Autores principales: Hema, Kanipakam, Ahamad, Shahzaib, Joon, Hemant Kumar, Pandey, Rajan, Gupta, Dinesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280665/
https://www.ncbi.nlm.nih.gov/pubmed/34278137
http://dx.doi.org/10.1021/acsomega.1c01988
_version_ 1783722683835351040
author Hema, Kanipakam
Ahamad, Shahzaib
Joon, Hemant Kumar
Pandey, Rajan
Gupta, Dinesh
author_facet Hema, Kanipakam
Ahamad, Shahzaib
Joon, Hemant Kumar
Pandey, Rajan
Gupta, Dinesh
author_sort Hema, Kanipakam
collection PubMed
description [Image: see text] Microtubules are tubulin polymers present in the eukaryotic cytoskeleton essential for structural stability and cell division that are also roadways for intracellular transport of vesicles and organelles. In the human malaria parasite Plasmodium falciparum, apart from providing structural stability and cell division, microtubules also facilitate important biological activities crucial for parasite survival in hosts, such as egression and motility. Hence, parasite structures and processes involving microtubules are among the most important drug targets for discovering much-needed novel Plasmodium inhibitors. The current study aims to construct reliable and high-quality 3D models of α-, β-, and γ-tubulins using various modeling techniques. We identified a common binding pocket specific to Plasmodium α-, β-, and γ-tubulins. Molecular dynamics simulations confirmed the stability of the Plasmodium tubulin 3D structures. The models generated in the present study may be used for protein–protein and protein–drug interaction investigations targeted toward designing malaria parasite tubulin-specific inhibitors.
format Online
Article
Text
id pubmed-8280665
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-82806652021-07-16 Atomic Resolution Homology Models and Molecular Dynamics Simulations of Plasmodium falciparum Tubulins Hema, Kanipakam Ahamad, Shahzaib Joon, Hemant Kumar Pandey, Rajan Gupta, Dinesh ACS Omega [Image: see text] Microtubules are tubulin polymers present in the eukaryotic cytoskeleton essential for structural stability and cell division that are also roadways for intracellular transport of vesicles and organelles. In the human malaria parasite Plasmodium falciparum, apart from providing structural stability and cell division, microtubules also facilitate important biological activities crucial for parasite survival in hosts, such as egression and motility. Hence, parasite structures and processes involving microtubules are among the most important drug targets for discovering much-needed novel Plasmodium inhibitors. The current study aims to construct reliable and high-quality 3D models of α-, β-, and γ-tubulins using various modeling techniques. We identified a common binding pocket specific to Plasmodium α-, β-, and γ-tubulins. Molecular dynamics simulations confirmed the stability of the Plasmodium tubulin 3D structures. The models generated in the present study may be used for protein–protein and protein–drug interaction investigations targeted toward designing malaria parasite tubulin-specific inhibitors. American Chemical Society 2021-06-30 /pmc/articles/PMC8280665/ /pubmed/34278137 http://dx.doi.org/10.1021/acsomega.1c01988 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Hema, Kanipakam
Ahamad, Shahzaib
Joon, Hemant Kumar
Pandey, Rajan
Gupta, Dinesh
Atomic Resolution Homology Models and Molecular Dynamics Simulations of Plasmodium falciparum Tubulins
title Atomic Resolution Homology Models and Molecular Dynamics Simulations of Plasmodium falciparum Tubulins
title_full Atomic Resolution Homology Models and Molecular Dynamics Simulations of Plasmodium falciparum Tubulins
title_fullStr Atomic Resolution Homology Models and Molecular Dynamics Simulations of Plasmodium falciparum Tubulins
title_full_unstemmed Atomic Resolution Homology Models and Molecular Dynamics Simulations of Plasmodium falciparum Tubulins
title_short Atomic Resolution Homology Models and Molecular Dynamics Simulations of Plasmodium falciparum Tubulins
title_sort atomic resolution homology models and molecular dynamics simulations of plasmodium falciparum tubulins
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280665/
https://www.ncbi.nlm.nih.gov/pubmed/34278137
http://dx.doi.org/10.1021/acsomega.1c01988
work_keys_str_mv AT hemakanipakam atomicresolutionhomologymodelsandmoleculardynamicssimulationsofplasmodiumfalciparumtubulins
AT ahamadshahzaib atomicresolutionhomologymodelsandmoleculardynamicssimulationsofplasmodiumfalciparumtubulins
AT joonhemantkumar atomicresolutionhomologymodelsandmoleculardynamicssimulationsofplasmodiumfalciparumtubulins
AT pandeyrajan atomicresolutionhomologymodelsandmoleculardynamicssimulationsofplasmodiumfalciparumtubulins
AT guptadinesh atomicresolutionhomologymodelsandmoleculardynamicssimulationsofplasmodiumfalciparumtubulins