Single amino acid substitutions in Fibroblast Growth Factor Receptor 1 (FGFR1) destabilize protein and have been implicated in several genetic disorders like various forms of cancer, Kallamann syndrome, Pfeiffer syndrome, Jackson Weiss syndrome, etc. In order to gain functional insight into mutation caused by amino acid substitution to protein function and expression, special emphasis was laid on molecular dynamics simulation techniques in combination with in silico tools such as SIFT, PolyPhen 2.0, I-Mutant 3.0 and SNAP. It has been estimated that 68% nsSNPs were predicted to be deleterious by I-Mutant, slightly higher than SIFT (37%), PolyPhen 2.0 (61%) and SNAP (58%). From the observed results, P722S mutation was found to be most deleterious by comparing results of all in silico tools. By molecular dynamics approach, we have shown that P722S mutation leads to increase in flexibility, and deviated more from the native structure which was supported by the decrease in the number of hydrogen bonds. In addition, biophysical analysis revealed a clear insight of stability loss due to P722S mutation in FGFR1 protein. Majority of mutations predicted by these in silico tools were in good concordance with the experimental results.
The study investigated the phytochemical, cytotoxicity and antioxidant properties of Allamanda cathartica (AC), Bixa orellana (BO), Cymbopogon citratus (CC), Ficus exasperata (FE) and Momordica charantia (MC) used traditionally for the anti-malarial preparations "Agbo" in Nigeria. Phytochemical screening of the plants showed the presence of flavonoids, terpenoids, phenolics, cardiac glycosides and reducing sugars. Free radical scavenging activity of the plants with 2, 2-Diphenyl-1-Picrylhydrazyl (DPPH) recorded significant IC 50 values for the inhibition of DPPH by ethanolic leaves extracts of AC (0.46), BO (0.45), CC (1.35) and FE (0.86), respectively and Vit. E (control), recorded higher activity at 0.5 mg mLG 1 with an IC 50 of 0.25 μg mLG 1. BO leaf extracts recorded the most potent effect (0.45) at low concentration of 0.5 mg mLG 1. The free radical scavenging activities of these plants doubtlessly contribute to their use in indigenous malaria therapy and may qualify them for anti-malarial drug screening.
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