Riboswitch can bind small molecules to regulate gene expression. Unlike other RNAs, riboswitch relies on its conformational switching for regulation. However, the understanding of the switching mechanism is still limited. Here, we focussed on the add A-riboswitch to illustrate the dynamical switching mechanism as an example. We performed molecular dynamics simulation, conservation and co-evolution calculations to infer the dynamical motions and evolutionary base pairings. The results suggest that the binding domain is stable for molecule recognition and binding, whereas the switching base pairings are co-evolutionary for translation. The understanding of the add A-riboswitch switching mechanism provides a potential solution for riboswitch drug design.
The single crystal XRD analysis has been used to examine the structure of the centrosymmetric crystal 4-Methoxy acetanilide. The material delineated in orthorhombic system with the space group of Pbca. FTIR and Raman spectrum analysis have been executed to comprehend the molecular interactions and to study the vibrational nature of the functional groups presented in the title molecule. Characteristic studies like optical, dielectric and thermal stability have also been carried out. Detailed explorations have been conducted on the optical properties of the crystal using both quantum chemical calculations and experimental data.
One quarter of the world’s population are infected by Mycobacterium tuberculosis (Mtb), which is a leading death-causing bacterial pathogen. Recent evidence has demonstrated that two virulence factors, ESAT-6 and CFP-10, play crucial roles in Mtb’s cytosolic translocation. Many efforts have been made to study the ESAT-6 and CFP-10 proteins. Some studies have shown that ESAT-6 has an essential role in rupturing phagosome. However, the mechanisms of how ESAT-6 interacts with the membrane have not yet been fully understood. Recent studies indicate that the ESAT-6 disassociates with CFP-10 upon their interaction with phagosome membrane, forming a membrane-spanning pore. Based on these observations, as well as the available structure of ESAT-6, ESAT-6 is hypothesized to form an oligomer for membrane insertion as well as rupturing. Such an ESAT-6 oligomer may play a significant role in the tuberculosis infection. Therefore, deeper understanding of the oligomerization of ESAT-6 will establish new directions for tuberculosis treatment. However, the structure of the oligomer of ESAT-6 is not known. Here, we proposed a comprehensive approach to model the complex structures of ESAT-6 oligomer inside a membrane. Several computational tools, including MD simulation, symmetrical docking, MM/PBSA, are used to obtain and characterize such a complex structure. Results from our studies lead to a well-supported hypothesis of the ESAT-6 oligomerization as well as the identification of essential residues in stabilizing the ESAT-6 oligomer which provide useful insights for future drug design targeting tuberculosis. The approach in this research can also be used to model and study other cross-membrane complex structures.
This study is based on the valuation of a few model molecules. The objective of this research is focussed on the nonlinear optical (NLO) improvement of four organometallic molecules and one organic molecule. These molecules have been subjected to several calculations by different functionals: CAM–B3LYP, LC–BLYP, LC–wPBE, wB97X, M11, M06–2X, M08–HX and M08–SO. These functionals gave three orders of classification of the [Formula: see text] parameters. The CAM–B3LYP functional recorded very good agreement between [Formula: see text] parameters and gaps ([Formula: see text]. Significant first hyperpolarizabilities ([Formula: see text] have been obtained around 880 * 10[Formula: see text][Formula: see text]esu. The mechanisms of intramolecular charge transfer (ICT) have shown energetic passages from donor groups to acceptors and vice versa. The substitution of metals influences the location of [Formula: see text] electrons at the level of the chromophores. Finally, the lengthening of the aromatic chains between the acceptor and donor groups shows significant NLO improvements. The first and second hyperpolarizabilities ([Formula: see text] and ([Formula: see text] for a chain of several benzene rings are of the order of 21,663.16 * 10[Formula: see text][Formula: see text]esu and 16,464.65 * 10[Formula: see text][Formula: see text]esu, respectively.
Xanthine Oxidoreductase (XOR) exists in a variety of organisms from bacteria to humans and catalyzes the oxidation of hypoxanthine to xanthine and from xanthine to uric acid. Excessive uric acid could lead to gout and hyperuricemia. In this paper, we have reviewed the recent computational studies on xanthine oxidase inhibition. Computational methods, such as molecular dynamics (molecular mechanics), quantum mechanics, and quantum mechanics/molecular mechanics (QM/MM), have been employed to investigate the binding affinity of xanthine oxidase with synthesized and isolated nature inhibitors. The limitations of different computational methods for xanthine oxidase inhibition studies were also discussed. Implications of the computational approach could be used to help to understand the existing arguments on substrate/product orientation in xanthine oxidase inhibition, which allows designing new inhibitors with higher efficacy.
