Browsing by Author "Mudogo, Celestin"

Now showing 1 - 3 of 3

A computer-based approach for developing linamarase inhibitory agents
(Walter de Gruyter GmbH, 2020-04-18) Paul, Lucas; Mudogo, Celestin; Mtei, Kelvin; Machunda, Revocatus; Ntie-Kang, Fidele
Cassava is a strategic crop, especially for developing countries. However, the presence of cyanogenic compounds in cassava products limits the proper nutrients utilization. Due to the poor availability of structure discovery and elucidation in the Protein Data Bank is limiting the full understanding of the enzyme, how to inhibit it and applications in different fields. There is a need to solve the three-dimensional structure (3-D) of linamarase from cassava. The structural elucidation will allow the development of a competitive inhibitor and various industrial applications of the enzyme. The goal of this review is to summarize and present the available 3-D modeling structure of linamarase enzyme using different computational strategies. This approach could help in determining the structure of linamarase and later guide the structure elucidation in silico and experimentally
A Molecular Investigation of the Solvent Influence on Inter- and Intra-Molecular Hydrogen Bond Interaction of Linamarin
(MDPI, 2022-02-11) Paul, Lucas; Deogratias, Geradius; Shadrack, Daniel; Mudogo, Celestin; Mtei, Kelvin; Machunda, Revocatus; Paluch, Andrew; Ntie‐Kang, Fidele
Linamarin has been reported to have anticancer activities; however, its extraction and isolation using different solvents yield a low amount. Therefore, understanding the physical prop‐ erties, such as solvents’ solubility, membrane permeability and lipophilicity and how they are asso‐ ciated with different solvents, is a paramount topic for discussion, especially for its potential as a drug. Linamarin has a sugar moiety with many polar groups responsible for its physical properties. Following current trends, a molecular dynamics simulation is performed to investigate its physical properties and how different solvents, such as water, methanol (MeOH), dimethyl sulfoxide (DMSO) and dichloromethane (DCM), affect such properties. In this work, we have investigated the influence of intermolecular and intramolecular hydrogen bonding and the influence of polar and non‐polar solvents on the physical properties of linamarin. Furthermore, solvation free‐energy and electronic structure analysis are performed. The structural analysis results show that the polar groups of linamarin have strong interactions with all solvents except the etheric oxygen groups. A detailed analysis shows intermolecular hydrogen bonding between polar solvents (water, MeOH and DMSO) and the hydroxyl oxygens of linamarin. Water exhibits the strongest interaction with linamarin’s functional groups among the investigated solvents. The findings show that within the first solvation shell, the number of water molecules is greatest, while MeOH has the fewest. Cen‐ trally to the structural analysis, solvation free energy confirms DMSO to be the best solvent since it prefers to interact with linamarin over itself, while water prefers to interact with itself. While the solute–solvent interactions are strongest between linamarin and water, the solvent–solvent interac‐ tions are strongest in water. As a result, the solvation free‐energy calculations reveal that linamarin solvation is most favourable in DMSO.
Structural characterization of cassava linamarase-linamarin enzyme complex: an integrated computational approach
(Taylor & Francis Group, 2021-05-21) Paul, Lucas; Shadrack, Daniel; Mudogo, Celestin; Mtei, Kelvin; Machunda, Revocatus; Ntie‐Kang, Fidele
Cassava linamarase is a hydrolyzing enzyme that belongs to a glycoside hydrolase family 1 (GH1). It is responsible for breaking down linamarin to toxic cyanide. The enzyme provides a defensive mechanism for plants against herbivores and has various applications in many fields. Understanding the structure of linamarase at the molecular level is a key to avail its reaction mechanism. In this study, the three-dimensional (3D) structure of linamarase was built for the first time using homology modelling and used to study its interaction with linamarin. Molecular docking calculations established the binding and orientation nature of linamarin, while molecular dynamics (MD) simulation established protein-ligand complexes' stability. Binding-free energy based on MM/PBSA was further used to rescore the docking results. An ensemble structure was found to be relatively stable compared to the modelled structure. This study sheds light on the exploration of linamarase towards understanding its reaction mechanisms.