Molecular simulation of protein-ligand complexes
Computational methods provide important contributions to modern drug discovery projects. In this thesis, we discuss the insights into protein-ligand interactions afforded by methods such as molecular docking, molecular dynamics (MD) and alchemical free energy calculations, which expedite the process...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
| Published: |
2022
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| Online Access: | https://eprints.nottingham.ac.uk/68947/ |
| _version_ | 1848800517913837568 |
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| author | Guest, Ellen |
| author_facet | Guest, Ellen |
| author_sort | Guest, Ellen |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Computational methods provide important contributions to modern drug discovery projects. In this thesis, we discuss the insights into protein-ligand interactions afforded by methods such as molecular docking, molecular dynamics (MD) and alchemical free energy calculations, which expedite the process of lead compound design and optimisation. These methods are applied to two case studies of biomolecular systems of therapeutic interest. The targets of the studies are the integrin αvβ6 and the bromodomain-containing protein 4 (BRD4). As the accuracy of molecular mechanics based methods relies on the quality of the force field in which the potential energy is calculated from, we focus on developing force field parameters for a series of small molecule inhibitors of αvβ6. Parameters are then applied to MD and relative free energy perturbation (FEP) simulations. MD simulations highlight the importance of hydrogen bonds, metal chelate interactions and cation- |
| first_indexed | 2025-11-14T20:52:50Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-68947 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:52:50Z |
| publishDate | 2022 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-689472022-08-02T04:40:23Z https://eprints.nottingham.ac.uk/68947/ Molecular simulation of protein-ligand complexes Guest, Ellen Computational methods provide important contributions to modern drug discovery projects. In this thesis, we discuss the insights into protein-ligand interactions afforded by methods such as molecular docking, molecular dynamics (MD) and alchemical free energy calculations, which expedite the process of lead compound design and optimisation. These methods are applied to two case studies of biomolecular systems of therapeutic interest. The targets of the studies are the integrin αvβ6 and the bromodomain-containing protein 4 (BRD4). As the accuracy of molecular mechanics based methods relies on the quality of the force field in which the potential energy is calculated from, we focus on developing force field parameters for a series of small molecule inhibitors of αvβ6. Parameters are then applied to MD and relative free energy perturbation (FEP) simulations. MD simulations highlight the importance of hydrogen bonds, metal chelate interactions and cation- 2022-08-02 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/68947/1/thesis_corrected.pdf Guest, Ellen (2022) Molecular simulation of protein-ligand complexes. PhD thesis, University of Nottingham. Protein-ligand complexes Molecular simulation |
| spellingShingle | Protein-ligand complexes Molecular simulation Guest, Ellen Molecular simulation of protein-ligand complexes |
| title | Molecular simulation of protein-ligand complexes |
| title_full | Molecular simulation of protein-ligand complexes |
| title_fullStr | Molecular simulation of protein-ligand complexes |
| title_full_unstemmed | Molecular simulation of protein-ligand complexes |
| title_short | Molecular simulation of protein-ligand complexes |
| title_sort | molecular simulation of protein-ligand complexes |
| topic | Protein-ligand complexes Molecular simulation |
| url | https://eprints.nottingham.ac.uk/68947/ |