Bioactive compounds from Morchella esculenta as potential inhibitors of RNA-binding protein La in ovarian cancer: a molecular modeling and quantum mechanics approach.

La protein is significantly expressed in various malignant tumors, including ovarian cancer (OC), which is related to the poor response to platinum-based chemotherapy. Thus, inhibiting La protein could control the expression of the potential downstream genes involved in promoting proliferation and chemotherapy resistance to OC, which could serve as a therapeutic intervention. Through a molecular docking approach, 12 compounds from Morchella esculenta were screened against the crystal structure of La protein and four hit compounds were identified, including beta-carotene, p-hydroxybenzoic acid, gamma-tocopherol, and alpha-tocopherol, with a binding affinity of - 10.7, - 8.1, - 7.9, and - 7.6 kcal/mol, respectively, higher than pyridine-2-carboxylate (control), with a binding affinity of - 5.2 kcal/mol. To explore the interaction of the hit compounds with the target receptor, they were selected for a molecular dynamic simulation and post-simulation analysis for 100 ns. The result showed promising reliability of the ligands due to a stable interaction with the La protein crystal structure. Furthermore, the drug-likeness and physicochemical chemical properties of the compounds were investigated using ADMET study and density functional theory analysis, respectively, and the result shows that the hit compounds could serve as a promising starting for the development of novel LA protein inhibitors for OC therapeutics. Finally, this study compared HOMO and LUMO values from global hybrids with long-range corrected DFAs, and the result from the two followed the same qualitative pattern while calculating HOMO values; however, MO62X/cc-pVTZ could better predict LUMO values when considering a global hybrid.

The molecular basis of color vision in colorful fish: four long wave-sensitive (LWS) opsins in guppies (Poecilia reticulata) are defined by amino acid substitutions at key functional sites.

BACKGROUND: Comparisons of functionally important changes at the molecular level in model systems have identified key adaptations driving isolation and speciation. In cichlids, for example, long wavelength-sensitive (LWS) opsins appear to play a role in mate choice and male color variation within and among species. To test the hypothesis that the evolution of elaborate coloration in male guppies (Poecilia reticulata) is also associated with opsin gene diversity, we sequenced long wavelength-sensitive (LWS) opsin genes in six species of the family Poeciliidae. RESULTS: Sequences of four LWS opsin genes were amplified from the guppy genome and from mRNA isolated from adult guppy eyes. Variation in expression was quantified using qPCR. Three of the four genes encode opsins predicted to be most sensitive to different wavelengths of light because they vary at key amino acid positions. This family of LWS opsin genes was produced by a diversity of duplication events. One, an intronless gene, was produced prior to the divergence of families Fundulidae and Poeciliidae. Between-gene PCR and DNA sequencing show that two of the guppy LWS opsins are linked in an inverted orientation. This inverted tandem duplication event occurred near the base of the poeciliid tree in the common ancestor of Poecilia and Xiphophorus. The fourth sequence has been uncovered only in the genus Poecilia. In the guppies surveyed here, this sequence is a hybrid, with the 5' end most similar to one of the tandem duplicates and the 3' end identical to the other. CONCLUSION: Enhanced wavelength discrimination, a possible consequence of opsin gene duplication and divergence, might have been an evolutionary prerequisite for color-based sexual selection and have led to the extraordinary coloration now observed in male guppies and in many other poeciliids.