The determination of CHARMM force field parameters for the Mg2+ containing HIV-1 integrase:
- Musyoka, Thommas M, Tastan Bishop, Özlem, Lobb, Kevin A, Moses, Vuyani
- Authors: Musyoka, Thommas M , Tastan Bishop, Özlem , Lobb, Kevin A , Moses, Vuyani
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148139 , vital:38713 , DOI: 10.1016/j.cplett.2018.09.019
- Description: The HIV integrase enzyme is a validated drug target. However, its potential has remained largely unexploited until recently due to lack of structural and mechanistic information. Its catalytic core domain (CCD) is crucial for the viral-human DNA integration making integrase an ideal target for inhibitor design. However, in order to do so, force field parameters for the integrase magnesium ion need to be established. Quantum mechanical calculations were used to derive force field parameters which were validated through molecular dynamics studies. Our results show that the parameters determined accurately maintain the integrity of the metal pocket of the integrase CCD.
- Full Text:
- Authors: Musyoka, Thommas M , Tastan Bishop, Özlem , Lobb, Kevin A , Moses, Vuyani
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148139 , vital:38713 , DOI: 10.1016/j.cplett.2018.09.019
- Description: The HIV integrase enzyme is a validated drug target. However, its potential has remained largely unexploited until recently due to lack of structural and mechanistic information. Its catalytic core domain (CCD) is crucial for the viral-human DNA integration making integrase an ideal target for inhibitor design. However, in order to do so, force field parameters for the integrase magnesium ion need to be established. Quantum mechanical calculations were used to derive force field parameters which were validated through molecular dynamics studies. Our results show that the parameters determined accurately maintain the integrity of the metal pocket of the integrase CCD.
- Full Text:
The evaluation and validation of copper (II) force field parameters of the Auxiliary Activity family 9 enzymes:
- Moses, Vuyani, Tastan Bishop, Özlem, Lobb, Kevin A
- Authors: Moses, Vuyani , Tastan Bishop, Özlem , Lobb, Kevin A
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148206 , vital:38719 , DOI: 10.1016/j.cplett.2017.04.022
- Description: The Auxiliary Activity family 9 (AA9) proteins are Cu2+ coordinating enzymes which are crucial for the early stages of cellulose degradation. In this study, the force field parameters for copper-containing bonds in the Type 1 AA9 protein active site were established and used in a molecular dynamics simulation on a solvated, neutralized system containing an AA9 protein, Cu2+ and a β-cellulose surface. The copper to cellulose interaction was evident during the dynamics, which could also be accelerated by the use of high Cu O van der Waals parameters. The interaction of AA9, Cu2+ and cellulose is described in detail.
- Full Text:
- Authors: Moses, Vuyani , Tastan Bishop, Özlem , Lobb, Kevin A
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/148206 , vital:38719 , DOI: 10.1016/j.cplett.2017.04.022
- Description: The Auxiliary Activity family 9 (AA9) proteins are Cu2+ coordinating enzymes which are crucial for the early stages of cellulose degradation. In this study, the force field parameters for copper-containing bonds in the Type 1 AA9 protein active site were established and used in a molecular dynamics simulation on a solvated, neutralized system containing an AA9 protein, Cu2+ and a β-cellulose surface. The copper to cellulose interaction was evident during the dynamics, which could also be accelerated by the use of high Cu O van der Waals parameters. The interaction of AA9, Cu2+ and cellulose is described in detail.
- Full Text:
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