Transformation of transmembrane proteins into soluble forms using protein language models

Redesigning insoluble proteins into soluble forms is crucial for advancing studies on protein structure, function, and interactions. Redesigning proteins in vitro without the aid of computational tools would necessitate substantial time and resources. This project aims to redesign the transmembrane...

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Bibliographic Details
Main Author: Lim, Si Ni
Other Authors: Mu Yuguang
Format: Final Year Project (FYP)
Language:English
Published: Nanyang Technological University 2024
Subjects:
Online Access:https://hdl.handle.net/10356/179523
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author Lim, Si Ni
author2 Mu Yuguang
author_facet Mu Yuguang
Lim, Si Ni
author_sort Lim, Si Ni
collection NTU
description Redesigning insoluble proteins into soluble forms is crucial for advancing studies on protein structure, function, and interactions. Redesigning proteins in vitro without the aid of computational tools would necessitate substantial time and resources. This project aims to redesign the transmembrane domain of Outer Membrane Protein A (OmpA) from Escherichia coli into a soluble form using computational tools such as ProteinMPNN, Protein-Sol and AlphaFold 3. Hydrophobic surface residues and its were identified on OmpA and redesigned using ProteinMPNN. The sequences generated were then ran through Protein-Sol and AlphaFold to predict its solubility and structure. The results indicate a theoretical increase in solubility of up to 35% and demonstrate that the redesigned protein can achieve a β-barrel structure, characteristic of OmpA, with high confidence, as predicted by computational software. However, experimental validation is required to confirm these in silico findings.
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spelling ntu-10356/1795232024-08-12T15:33:01Z Transformation of transmembrane proteins into soluble forms using protein language models Lim, Si Ni Mu Yuguang School of Biological Sciences YGMu@ntu.edu.sg Medicine, Health and Life Sciences Protein design Computational Redesigning insoluble proteins into soluble forms is crucial for advancing studies on protein structure, function, and interactions. Redesigning proteins in vitro without the aid of computational tools would necessitate substantial time and resources. This project aims to redesign the transmembrane domain of Outer Membrane Protein A (OmpA) from Escherichia coli into a soluble form using computational tools such as ProteinMPNN, Protein-Sol and AlphaFold 3. Hydrophobic surface residues and its were identified on OmpA and redesigned using ProteinMPNN. The sequences generated were then ran through Protein-Sol and AlphaFold to predict its solubility and structure. The results indicate a theoretical increase in solubility of up to 35% and demonstrate that the redesigned protein can achieve a β-barrel structure, characteristic of OmpA, with high confidence, as predicted by computational software. However, experimental validation is required to confirm these in silico findings. Bachelor's degree 2024-08-07T00:37:39Z 2024-08-07T00:37:39Z 2024 Final Year Project (FYP) Lim, S. N. (2024). Transformation of transmembrane proteins into soluble forms using protein language models. Final Year Project (FYP), Nanyang Technological University, Singapore. https://hdl.handle.net/10356/179523 https://hdl.handle.net/10356/179523 en application/pdf Nanyang Technological University
spellingShingle Medicine, Health and Life Sciences
Protein design
Computational
Lim, Si Ni
Transformation of transmembrane proteins into soluble forms using protein language models
title Transformation of transmembrane proteins into soluble forms using protein language models
title_full Transformation of transmembrane proteins into soluble forms using protein language models
title_fullStr Transformation of transmembrane proteins into soluble forms using protein language models
title_full_unstemmed Transformation of transmembrane proteins into soluble forms using protein language models
title_short Transformation of transmembrane proteins into soluble forms using protein language models
title_sort transformation of transmembrane proteins into soluble forms using protein language models
topic Medicine, Health and Life Sciences
Protein design
Computational
url https://hdl.handle.net/10356/179523
work_keys_str_mv AT limsini transformationoftransmembraneproteinsintosolubleformsusingproteinlanguagemodels