Molecular docking and molecular dynamics simulation of mutant carboxylesterase in enhancing microplastics binding affinity

Literature survey has shown that microbial and biodegradation of polyethylene terephthalate (PET) by PETases are eco-friendly. However, microbes capable of such feat are few in conjunction with being time-consuming and the laborious bioprospecting efforts are undesirable. Therefore, mutation by in s...

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Main Author:	Lameh, Fatana
Format:	Thesis
Language:	English
Published:	2021
Subjects:	Q Science (General)
Online Access:	http://eprints.utm.my/id/eprint/102448/1/FatanaLamehMFS2021.pdf.pdf
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spelling	my-utm-ep.1024482023-08-28T06:42:17Z Molecular docking and molecular dynamics simulation of mutant carboxylesterase in enhancing microplastics binding affinity 2021 Lameh, Fatana Q Science (General) Literature survey has shown that microbial and biodegradation of polyethylene terephthalate (PET) by PETases are eco-friendly. However, microbes capable of such feat are few in conjunction with being time-consuming and the laborious bioprospecting efforts are undesirable. Therefore, mutation by in silico means of current isomer of PETase to introduce PET degradative capability could be a better approach to resolve this issue. Previously, BTA-hydrolase was reported capable of degrading PET. This study aimed to convert a carboxylesterase from Archaeoglobus fulgidus (AFEST) to BTA-hydrolase of Thermobifida fusca by in silico site-directed mutagenesis of six amino acids. This was followed by molecular docking analysis with PET and polypropylene (PP) to compare their interactions. The best-docked enzyme-substrate complex was further subjected to molecular dynamics (MD) simulation using GROMACS to gauge the binding quality of the above-said proteins PET. Results of molecular docking revealed the mutated residues, Glu34Asn, Gly177Lys, Asp179 Ala, Leu120Phe, Ala168 Met, and Leu82Thr on the AFEST yielded the lowest binding energy for the wild-type AFEST-PP complex (-7.5 kcal/mol), followed by mutant AFEST-PP complex (-7.1 kcal/mol) and lastly, the BTA-hydrolase-PP complex with (-5.9 kcal/mol). The mutant-AFEST also showed lower binding energy (- 6.7 kcal/mol) than BTA-hydrolase (-5.6 kcal/mol) when complexed with PET. The energy-minimized wild-type-, mutant-AFEST and BTA-hydrolase docked ligand complexes showed that the RMSD value for the BTA-hydrolase-PET complex was stable (0.12 – 0.18 nm) after 5 ns compared to the mutant AFEST-PET complex (~0.22 nm) after 18 ns. The RMSF for the mutant AFEST-PET complex fluctuated at 0.43 nm for the mutated residue Lys177, while the RMSF value of the BTA-hydrolase-PET complex was 0.32 nm for Leu248. Finally, the Rg value for BTA-hydrolase-PET complex (~1.68 nm) was the lowest compared to the mutant-AFEST-PET and wild-type AFEST-PET complexes which both showed the same range (~1.80 – 1.84 nm). The collective in silico data conveyed the six residue mutations on the wild-type AFEST imparted a minimal change in the ability of the mutant-AFEST to bind to PET. This suggests that amino acid mutations that are closer and more centrally-located in the tunnel leading up to the catalytic site might yield a mutant-AFEST with better PET-degrading ability. 2021 Thesis http://eprints.utm.my/id/eprint/102448/ http://eprints.utm.my/id/eprint/102448/1/FatanaLamehMFS2021.pdf.pdf application/pdf en public http://dms.library.utm.my:8080/vital/access/manager/Repository/vital:146232 masters Universiti Teknologi Malaysia Faculty of Science
institution	Universiti Teknologi Malaysia
collection	UTM Institutional Repository
language	English
topic	Q Science (General)
spellingShingle	Q Science (General) Lameh, Fatana Molecular docking and molecular dynamics simulation of mutant carboxylesterase in enhancing microplastics binding affinity
description	Literature survey has shown that microbial and biodegradation of polyethylene terephthalate (PET) by PETases are eco-friendly. However, microbes capable of such feat are few in conjunction with being time-consuming and the laborious bioprospecting efforts are undesirable. Therefore, mutation by in silico means of current isomer of PETase to introduce PET degradative capability could be a better approach to resolve this issue. Previously, BTA-hydrolase was reported capable of degrading PET. This study aimed to convert a carboxylesterase from Archaeoglobus fulgidus (AFEST) to BTA-hydrolase of Thermobifida fusca by in silico site-directed mutagenesis of six amino acids. This was followed by molecular docking analysis with PET and polypropylene (PP) to compare their interactions. The best-docked enzyme-substrate complex was further subjected to molecular dynamics (MD) simulation using GROMACS to gauge the binding quality of the above-said proteins PET. Results of molecular docking revealed the mutated residues, Glu34Asn, Gly177Lys, Asp179 Ala, Leu120Phe, Ala168 Met, and Leu82Thr on the AFEST yielded the lowest binding energy for the wild-type AFEST-PP complex (-7.5 kcal/mol), followed by mutant AFEST-PP complex (-7.1 kcal/mol) and lastly, the BTA-hydrolase-PP complex with (-5.9 kcal/mol). The mutant-AFEST also showed lower binding energy (- 6.7 kcal/mol) than BTA-hydrolase (-5.6 kcal/mol) when complexed with PET. The energy-minimized wild-type-, mutant-AFEST and BTA-hydrolase docked ligand complexes showed that the RMSD value for the BTA-hydrolase-PET complex was stable (0.12 – 0.18 nm) after 5 ns compared to the mutant AFEST-PET complex (~0.22 nm) after 18 ns. The RMSF for the mutant AFEST-PET complex fluctuated at 0.43 nm for the mutated residue Lys177, while the RMSF value of the BTA-hydrolase-PET complex was 0.32 nm for Leu248. Finally, the Rg value for BTA-hydrolase-PET complex (~1.68 nm) was the lowest compared to the mutant-AFEST-PET and wild-type AFEST-PET complexes which both showed the same range (~1.80 – 1.84 nm). The collective in silico data conveyed the six residue mutations on the wild-type AFEST imparted a minimal change in the ability of the mutant-AFEST to bind to PET. This suggests that amino acid mutations that are closer and more centrally-located in the tunnel leading up to the catalytic site might yield a mutant-AFEST with better PET-degrading ability.
format	Thesis
qualification_level	Master's degree
author	Lameh, Fatana
author_facet	Lameh, Fatana
author_sort	Lameh, Fatana
title	Molecular docking and molecular dynamics simulation of mutant carboxylesterase in enhancing microplastics binding affinity
title_short	Molecular docking and molecular dynamics simulation of mutant carboxylesterase in enhancing microplastics binding affinity
title_full	Molecular docking and molecular dynamics simulation of mutant carboxylesterase in enhancing microplastics binding affinity
title_fullStr	Molecular docking and molecular dynamics simulation of mutant carboxylesterase in enhancing microplastics binding affinity
title_full_unstemmed	Molecular docking and molecular dynamics simulation of mutant carboxylesterase in enhancing microplastics binding affinity
title_sort	molecular docking and molecular dynamics simulation of mutant carboxylesterase in enhancing microplastics binding affinity
granting_institution	Universiti Teknologi Malaysia
granting_department	Faculty of Science
publishDate	2021
url	http://eprints.utm.my/id/eprint/102448/1/FatanaLamehMFS2021.pdf.pdf
_version_	1776100925408018432

Molecular docking and molecular dynamics simulation of mutant carboxylesterase in enhancing microplastics binding affinity

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