Allosteric site modulators: a case study for falcipains as malarial drug targets
- Musyoka, Thommas, Tastan Bishop, Özlem
- Authors: Musyoka, Thommas , Tastan Bishop, Özlem
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162699 , vital:40974 , https://doi.org/10.21955/gatesopenres.1116459.1
- Description: Fighting against malaria is a never-ending battle. Plasmodium parasites continuously develop resistance to the drugs used against them including the artemisinin-based combination therapies as observed recently in Southeast Asia. The main concern now is whether the resistant parasite strains spread to Africa, where most malaria cases are located. To prevent this, we need to think outside the box. To date, there is no allosteric drug for malaria. Hence, allosteric drug targeting sites and modulators might be a new hope for malarial treatment. In Plasmodium falciparum two cysteine proteases, falcipain-2 (FP-2) and falcipain-3 (FP-3), have been identified as the main hemoglobinases, and are considered as attractive drug targets.
- Full Text:
- Date Issued: 2019
- Authors: Musyoka, Thommas , Tastan Bishop, Özlem
- Date: 2019
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/162699 , vital:40974 , https://doi.org/10.21955/gatesopenres.1116459.1
- Description: Fighting against malaria is a never-ending battle. Plasmodium parasites continuously develop resistance to the drugs used against them including the artemisinin-based combination therapies as observed recently in Southeast Asia. The main concern now is whether the resistant parasite strains spread to Africa, where most malaria cases are located. To prevent this, we need to think outside the box. To date, there is no allosteric drug for malaria. Hence, allosteric drug targeting sites and modulators might be a new hope for malarial treatment. In Plasmodium falciparum two cysteine proteases, falcipain-2 (FP-2) and falcipain-3 (FP-3), have been identified as the main hemoglobinases, and are considered as attractive drug targets.
- Full Text:
- Date Issued: 2019
The determination of CHARMM force field parameters for the Mg2+ containing HIV-1 integrase:
- Musyoka, Thommas, Tastan Bishop, Özlem, Lobb, Kevin A, Moses, Vuyani
- Authors: Musyoka, Thommas , 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:
- Date Issued: 2018
- Authors: Musyoka, Thommas , 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:
- Date Issued: 2018
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