AI-Based Homology Modelling of Fatty Acid Transport Protein 1 Using AlphaFold: Structural Elucidation and Molecular Dynamics Exploration
Fatty acid transport protein 1 (FATP1) is an integral transmembrane protein that is involved in facilitating the translocation of long-chain fatty acids (LCFA) across the plasma membrane, thereby orchestrating the importation of LCFA into the cell. FATP1 also functions as an acyl-CoA ligase, catalyz...
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MDPI AG
2023-11-01
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| Series: | Biomolecules |
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| author | Ranjitha Acharya Shilpa S. Shetty Gollapalli Pavan Flama Monteiro Manne Munikumar Sriram Naresh Nalilu Suchetha Kumari |
| author_facet | Ranjitha Acharya Shilpa S. Shetty Gollapalli Pavan Flama Monteiro Manne Munikumar Sriram Naresh Nalilu Suchetha Kumari |
| author_sort | Ranjitha Acharya |
| collection | DOAJ |
| description | Fatty acid transport protein 1 (FATP1) is an integral transmembrane protein that is involved in facilitating the translocation of long-chain fatty acids (LCFA) across the plasma membrane, thereby orchestrating the importation of LCFA into the cell. FATP1 also functions as an acyl-CoA ligase, catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and VLCFA (very-long-chain fatty acids) as substrates. It is expressed in various types of tissues and is involved in the regulation of crucial signalling pathways, thus playing a vital role in numerous physiological and pathological conditions. Structural insight about FATP1 is, thus, extremely important for understanding the mechanism of action of this protein and developing efficient treatments against its anomalous expression and dysregulation, which are often associated with pathological conditions such as breast cancer. As of now, there has been no prior prediction or evaluation of the 3D configuration of the human FATP1 protein, hindering a comprehensive understanding of the distinct functional roles of its individual domains. In our pursuit to unravel the structure of the most commonly expressed isoforms of FATP1, we employed the cutting-edge ALPHAFOLD 2 model for an initial prediction of the entire protein’s structure. This prediction was complemented by molecular dynamics simulations, focusing on the most promising model. We predicted the structure of FATP1 in silico and thoroughly refined and validated it using coarse and molecular dynamics in the absence of the complete crystal structure. Their relative dynamics revealed the different properties of the characteristic FATP1. |
| first_indexed | 2024-03-09T16:58:52Z |
| format | Article |
| id | doaj.art-aac00d9616e34280ab97e13d21bf4b14 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T16:58:52Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-aac00d9616e34280ab97e13d21bf4b142023-11-24T14:32:13ZengMDPI AGBiomolecules2218-273X2023-11-011311167010.3390/biom13111670AI-Based Homology Modelling of Fatty Acid Transport Protein 1 Using AlphaFold: Structural Elucidation and Molecular Dynamics ExplorationRanjitha Acharya0Shilpa S. Shetty1Gollapalli Pavan2Flama Monteiro3Manne Munikumar4Sriram Naresh5Nalilu Suchetha Kumari6Department of Biochemistry, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore 575018, IndiaCentral Research Laboratory, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore 575018, IndiaCentral Research Laboratory, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore 575018, IndiaDepartment of Biochemistry, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore 575018, IndiaClinical Division, ICMR-National Institute of Nutrition, Jamai-Osmania (Post), Hyderabad 500007, IndiaDepartment of Biochemistry, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore 575018, IndiaDepartment of Biochemistry, KS Hegde Medical Academy, Nitte (Deemed to be University), Mangalore 575018, IndiaFatty acid transport protein 1 (FATP1) is an integral transmembrane protein that is involved in facilitating the translocation of long-chain fatty acids (LCFA) across the plasma membrane, thereby orchestrating the importation of LCFA into the cell. FATP1 also functions as an acyl-CoA ligase, catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and VLCFA (very-long-chain fatty acids) as substrates. It is expressed in various types of tissues and is involved in the regulation of crucial signalling pathways, thus playing a vital role in numerous physiological and pathological conditions. Structural insight about FATP1 is, thus, extremely important for understanding the mechanism of action of this protein and developing efficient treatments against its anomalous expression and dysregulation, which are often associated with pathological conditions such as breast cancer. As of now, there has been no prior prediction or evaluation of the 3D configuration of the human FATP1 protein, hindering a comprehensive understanding of the distinct functional roles of its individual domains. In our pursuit to unravel the structure of the most commonly expressed isoforms of FATP1, we employed the cutting-edge ALPHAFOLD 2 model for an initial prediction of the entire protein’s structure. This prediction was complemented by molecular dynamics simulations, focusing on the most promising model. We predicted the structure of FATP1 in silico and thoroughly refined and validated it using coarse and molecular dynamics in the absence of the complete crystal structure. Their relative dynamics revealed the different properties of the characteristic FATP1.https://www.mdpi.com/2218-273X/13/11/1670molecular dynamic simulationsFATP1LCFAVLCFA |
| spellingShingle | Ranjitha Acharya Shilpa S. Shetty Gollapalli Pavan Flama Monteiro Manne Munikumar Sriram Naresh Nalilu Suchetha Kumari AI-Based Homology Modelling of Fatty Acid Transport Protein 1 Using AlphaFold: Structural Elucidation and Molecular Dynamics Exploration Biomolecules molecular dynamic simulations FATP1 LCFA VLCFA |
| title | AI-Based Homology Modelling of Fatty Acid Transport Protein 1 Using AlphaFold: Structural Elucidation and Molecular Dynamics Exploration |
| title_full | AI-Based Homology Modelling of Fatty Acid Transport Protein 1 Using AlphaFold: Structural Elucidation and Molecular Dynamics Exploration |
| title_fullStr | AI-Based Homology Modelling of Fatty Acid Transport Protein 1 Using AlphaFold: Structural Elucidation and Molecular Dynamics Exploration |
| title_full_unstemmed | AI-Based Homology Modelling of Fatty Acid Transport Protein 1 Using AlphaFold: Structural Elucidation and Molecular Dynamics Exploration |
| title_short | AI-Based Homology Modelling of Fatty Acid Transport Protein 1 Using AlphaFold: Structural Elucidation and Molecular Dynamics Exploration |
| title_sort | ai based homology modelling of fatty acid transport protein 1 using alphafold structural elucidation and molecular dynamics exploration |
| topic | molecular dynamic simulations FATP1 LCFA VLCFA |
| url | https://www.mdpi.com/2218-273X/13/11/1670 |
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