A5057417551- Research on Leishmaniasis Studies
- Protein Structure and Dynamics
- Trypanosoma species research and implications
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- Synthesis and Biological Evaluation
- Quinazolinone synthesis and applications
- RNA modifications and cancer
- Mass Spectrometry Techniques and Applications
- Cancer-related gene regulation
- Drug Transport and Resistance Mechanisms
- vaccines and immunoinformatics approaches
- Crystallography and molecular interactions
- X-ray Diffraction in Crystallography
- Erythrocyte Function and Pathophysiology
- Crystallization and Solubility Studies
- Insect Pest Control Strategies
- Epigenetics and DNA Methylation
- Biotechnology and Related Fields
- SARS-CoV-2 and COVID-19 Research
- Lipid Membrane Structure and Behavior
University of Dundee
2023-2025
University of Edinburgh
2020-2024
Wellcome Centre for Anti-Infectives Research
2023
Universidad Nacional Autónoma de México
2011-2019
Many proteins recognise other via mechanisms that involve the folding of intrinsically disordered regions upon complex formation. Here we investigate how selectivity a drug-like small molecule arises from its modulation protein disorder-to-order transition. Binding compound AM-7209 has been reported to confer order an 'lid' region oncoprotein MDM2. Calorimetric measurements revealed truncation lid MDM2 increases apparent dissociation constant 250-fold. By contrast, little effect on binding...
The selectivity and affinity of numerous protein-protein interactions depends upon the folding intrinsically disordered regions (IDRs) that accompanies complexation. Yet there are currently no guiding principles for a similar molecular recognition strategy aimed at design small-molecule modulators this category interactions. Herein, driving forces underpin selective ordering N-terminal ‘lid’ region oncoprotein MDM2 by small molecule AM-7209 were elucidated combination dynamics simulations,...
The maturation of the RNA cap involving guanosine N-7 methylation, catalyzed by HsRNMT (RNA guanine-7 methyltransferase)-RAM guanine-N7 methyltransferase activating subunit) complex, is currently under investigation as a novel strategy to combat PIK3CA mutant breast cancer. However, development effective drugs hindered limited understanding enzyme's mechanism and lack small molecule inhibitors. Following elucidation HsRNMT-RAM molecular mechanism, we report biophysical characterization two...
The selectivity and affinity of numerous protein-protein interactions is tuned via binding mechanisms that involve folding intrinsically disordered regions (IDRs) on complexation. Yet there are currently no guiding principles for a similar molecular recognition strategy aimed at the design small-molecule modulators interactions. Herein, driving forces underpin selective ordering N-terminal ‘lid’ region oncoprotein MDM2 by small molecule AM-7209 were elucidated combination dynamics...
There is a need for novel chemical matter phenotypic and target-based screens to find starting points drug discovery programmes in neglected infectious diseases non-hormonal contraceptives that disproportionately affect Low- Middle-Income Countries (LMICs). In some disease areas multiple of corporate other libraries have been carried out, giving rise valuable leading preclinical candidates. Whilst areas, little screening has out. Much against pathogens conducted phenotypically as there are...
An in-silico drug repurposing study was carried out to search for potential COVID-19 antiviral agents. A dataset of 1615 FDA-approved drugs docked in the active site SARS CoV-2 Main protease. subset top scoring hit compounds subjected follow-up molecular dynamics simulations further characterise predicted binding modes. The main findings are that Aliskiren, Capreomycin, Isovuconazonium, emerge as novel inhibitors. We also observed Ceftolozane, Cobicistat, Carfilzomib and Saquinavir...
The maturation of the RNA cap involving guanosine N-7 methylation, catalyzed by HsRNMT (RNA guanine-7 methyltransferase)-RAM guanine-N7 methyltransferase activating subunit) complex, is currently under investigation as a novel strategy to combat PIK3CA mutant breast cancer. However, development effective drugs hindered limited understanding enzyme's mechanism and lack small molecule inhibitors. Following elucidation HsRNMT-RAM molecular mechanism, we report biophysical characterization two...
Abstract Many proteins recognise other via mechanisms that involve the folding of intrinsically disordered regions upon complex formation. Here we investigate how selectivity a drug-like small molecule arises from its modulation protein disorder-to-order transition. Binding compound AM-7209 has been reported to confer order an ‘lid’ region oncoprotein MDM2. Calorimetric measurements revealed truncation lid MDM2 increases apparent dissociation constant 250-fold. By contrast, little effect on...
There is an urgency of finding molecules available to treat Leishmaniasis, which one the significant issues health in undeveloped countries. For that reason needed explore molecular diversity find novel scaffolds. Fluorinated and adamantane derivatives exhibit a formidable starting point. They are proved improve antileishmanial activity when attached already active as we have shown this paper. Particularly fluorinated methoxy ethoxy can increase its volume depending on number fluorine,...