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- Abhinand, P. A., et al.
(författare)
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Insights on the structural perturbations in human MTHFR Ala222Val mutant by protein modeling and molecular dynamics
- 2016
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Ingår i: Journal of Biomolecular Structure and Dynamics. - : Informa UK Limited. - 0739-1102 .- 1538-0254. ; 34:4, s. 892-905
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Tidskriftsartikel (refereegranskat)abstract
- Methylenetetrahydrofolate reductase (MTHFR) protein catalyzes the only biochemical reaction which produces methyltetrahydrofolate, the active form of folic acid essential for several molecular functions. The Ala222Val polymorphism of human MTHFR encodes a thermolabile protein associated with increased risk of neural tube defects and cardiovascular disease. Experimental studies have shown that the mutation does not affect the kinetic properties of MTHFR, but inactivates the protein by increasing flavin adenine dinucleotide (FAD) loss. The lack of completely solved crystal structure of MTHFR is an impediment in understanding the structural perturbations caused by the Ala222Val mutation; computational modeling provides a suitable alternative. The three-dimensional structure of human MTHFR protein was obtained through homology modeling, by taking the MTHFR structures from Escherichia coli and Thermus thermophilus as templates. Subsequently, the modeled structure was docked with FAD using Glide, which revealed a very good binding affinity, authenticated by a Glide XP score of-10.3983 (kcal mol-1). The MTHFR was mutated by changing Alanine 222 to Valine. The wild-type MTHFR-FAD complex and the Ala222Val mutant MTHFR-FAD complex were subjected to molecular dynamics simulation over 50 ns period. The average difference in backbone root mean square deviation (RMSD) between wild and mutant variant was found to be ~.11 Å. The greater degree of fluctuations in the mutant protein translates to increased conformational stability as a result of mutation. The FAD-binding ability of the mutant MTHFR was also found to be significantly lowered as a result of decreased protein grip caused by increased conformational flexibility. The study provides insights into the Ala222Val mutation of human MTHFR that induces major conformational changes in the tertiary structure, causing a significant reduction in the FAD-binding affinity.
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- Nishal, M., et al.
(författare)
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Significance of additive manufacturing amidst the pandemic
- 2023
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Ingår i: Materials Today. - : Elsevier BV. - 2214-7853. ; 72, s. 2540-2546
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Tidskriftsartikel (refereegranskat)abstract
- In the light of COVID-19 pandemic, a global shortage for Personnel Protective Equipment (PPE) led to the search for an alternative to fill the gap where additive manufacturing made necessary development of rapid design and adaptive filtering masks for local manufacturing using 3D printing to help the frontline workers. The review focuses on the utilization of antimicrobial materials in additive manufacturing with the use of bespoke design to facilitate and respond to the disruptions in the medical supply chain. Previous studies confirmed the age-old theory of copper as an antimicrobial material with contact killing properties. The antimicrobial properties of copper have been registered at the U.S. Environmental Protection Agency as the first solid antimicrobial material. Combining the properties of copper in a PLA (Polylactic Acid) filament as a nano composite, Copper-3D facilitates the antimicrobial properties to any 3D printed object. Provided this flexibility of 3D printing, the use of masks designed distinctively based on the 3D scan of an individual's facial structures as an efficient Personnel Protective Equipment is also addressed. Additive manufacturing as a support to the shortage of medical devices and a responsive method to the disruption in the supply chain is discussed.
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