In Silico Design And Constant-Ph Molecular Dynamics Study Of Human Igg1 Fc At Ph6.0 And Ph 7.5

The use of monoclonal antibody against various illnesses such as cancer, infectious diseases or autoimmune disorders has become a mainstream in the field of medical therapeutics. Specifically, the IgG1 with long serum half-life has led to its popular usage as a therapeutic drug scaffold where this p...

Full description

Saved in:

Bibliographic Details
Main Author:	Lim, Yee Ying
Format:	Thesis
Language:	English
Published:	2020
Subjects:	R5-920 Medicine (General)
Online Access:	http://eprints.usm.my/51601/1/LIM%20YEE%20YING%20-%20TESIS%20cut.pdf
Tags:	Add Tag No Tags, Be the first to tag this record!

id	my-usm-ep.51601
record_format	uketd_dc
spelling	my-usm-ep.516012022-02-21T08:50:17Z In Silico Design And Constant-Ph Molecular Dynamics Study Of Human Igg1 Fc At Ph6.0 And Ph 7.5 2020-06 Lim, Yee Ying R5-920 Medicine (General) The use of monoclonal antibody against various illnesses such as cancer, infectious diseases or autoimmune disorders has become a mainstream in the field of medical therapeutics. Specifically, the IgG1 with long serum half-life has led to its popular usage as a therapeutic drug scaffold where this property is related to the pH-dependent binding mechanism of IgG1 with FcRn. In this work, constant pH molecular dynamics (CpHMD) simulation setup was first established by testing against experimentally validated Fc-FcRn complex (Wildtype, MutAAA and MutYTE), associating and dissociating at pH 6.0 and pH 7.5, respectively. Binding free energy (ΔGBind) calculation via the MMGBSA approach was used to describe the binding affinity for the control complexes (Wildtype-, MutAAA- and MutYTE-FcRn) and have showed Fc variant MutYTE as the strongest FcRn binder at pH 6.0. To obtain alternative Fc design with better binding properties for FcRn, pH 6.0 single trajectory MutYTE-FcRn representing complex was extracted by MMTSB toolset clustering followed by SAAMBE server single point mutations imposed on the MutYTE Fc of the complex. Mutagenesis result suggested four Fc positions with improved binding energy (ΔG) for FcRn. They were all applied to maximize the binding effect for FcRn, resulting the new IgG1 Fc variant design, MutM4 (Asp294Ala/Thr254Phe/Pro257Trp/ Asp312Gly). 2020-06 Thesis http://eprints.usm.my/51601/ http://eprints.usm.my/51601/1/LIM%20YEE%20YING%20-%20TESIS%20cut.pdf application/pdf en public masters Universiti Sains Malaysia Institut Penyelidikan Perubatan Molekul
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	R5-920 Medicine (General)
spellingShingle	R5-920 Medicine (General) Lim, Yee Ying In Silico Design And Constant-Ph Molecular Dynamics Study Of Human Igg1 Fc At Ph6.0 And Ph 7.5
description	The use of monoclonal antibody against various illnesses such as cancer, infectious diseases or autoimmune disorders has become a mainstream in the field of medical therapeutics. Specifically, the IgG1 with long serum half-life has led to its popular usage as a therapeutic drug scaffold where this property is related to the pH-dependent binding mechanism of IgG1 with FcRn. In this work, constant pH molecular dynamics (CpHMD) simulation setup was first established by testing against experimentally validated Fc-FcRn complex (Wildtype, MutAAA and MutYTE), associating and dissociating at pH 6.0 and pH 7.5, respectively. Binding free energy (ΔGBind) calculation via the MMGBSA approach was used to describe the binding affinity for the control complexes (Wildtype-, MutAAA- and MutYTE-FcRn) and have showed Fc variant MutYTE as the strongest FcRn binder at pH 6.0. To obtain alternative Fc design with better binding properties for FcRn, pH 6.0 single trajectory MutYTE-FcRn representing complex was extracted by MMTSB toolset clustering followed by SAAMBE server single point mutations imposed on the MutYTE Fc of the complex. Mutagenesis result suggested four Fc positions with improved binding energy (ΔG) for FcRn. They were all applied to maximize the binding effect for FcRn, resulting the new IgG1 Fc variant design, MutM4 (Asp294Ala/Thr254Phe/Pro257Trp/ Asp312Gly).
format	Thesis
qualification_level	Master's degree
author	Lim, Yee Ying
author_facet	Lim, Yee Ying
author_sort	Lim, Yee Ying
title	In Silico Design And Constant-Ph Molecular Dynamics Study Of Human Igg1 Fc At Ph6.0 And Ph 7.5
title_short	In Silico Design And Constant-Ph Molecular Dynamics Study Of Human Igg1 Fc At Ph6.0 And Ph 7.5
title_full	In Silico Design And Constant-Ph Molecular Dynamics Study Of Human Igg1 Fc At Ph6.0 And Ph 7.5
title_fullStr	In Silico Design And Constant-Ph Molecular Dynamics Study Of Human Igg1 Fc At Ph6.0 And Ph 7.5
title_full_unstemmed	In Silico Design And Constant-Ph Molecular Dynamics Study Of Human Igg1 Fc At Ph6.0 And Ph 7.5
title_sort	in silico design and constant-ph molecular dynamics study of human igg1 fc at ph6.0 and ph 7.5
granting_institution	Universiti Sains Malaysia
granting_department	Institut Penyelidikan Perubatan Molekul
publishDate	2020
url	http://eprints.usm.my/51601/1/LIM%20YEE%20YING%20-%20TESIS%20cut.pdf
_version_	1747822086330515456

In Silico Design And Constant-Ph Molecular Dynamics Study Of Human Igg1 Fc At Ph6.0 And Ph 7.5

Similar Items