Journal of molecular graphics & modelling最新文献

The use of microbial insecticides is a promising approach to circumvent the toxic effects of chemical insecticides due to their eco-friendly nature and significant effectiveness. Beauveria bassiana strain ARSEF 2860 is a commercially used bioinsecticide that lives in a symbiont association with a variety of plants or crops. The insecticidal mechanism of this fungal strain is initiated by chitinases that degrade the chitin layer of the insects. Among these chitinases, a significant number of chitinases lack a distinct chitin-binding domain and thus have compromised catalytic efficiency. Engineering of these chitinases to enhance the chitin-binding can be a potential approach to develope high potential bioinsecticides. Present study deals with analysis of 96 mutants of the J5JGB8 chitinase of B. bassiana strain ARSEF 2860 to improve chitin-binding in the substrate binding cavity. In-silico site-directed mutagenesis revealed 30 mutations as stable, having an effective change in Gibb's free energy. Molecular docking of J5JGB8 chitinase and all stable mutants with chitin subunit proved significantly high negative binding energy of Ala127Ser mutant (-8.24 kcal/mol) compared to the wild-type enzyme (-6.75 kcal/mol). Molecular dynamic simulation analysis of Ala127Ser chitinase-chitin and wild-type chitinase-chitin complexes revealed higher number of hydrogen bonding in Ala127Ser chitinase-chitin complex, displaying high stability of chitin-binding in the substrate binding cavity of the mutant. End state free binding energy analysis showed effective change in electrostatic energy of the interactions stabilizing the binding of chitin at the substrate binding site of the Ala127Ser mutant J5JGB8 chitinase with respect to wild-type confirming improved binding of chitin with the mutant chitinase. Hence, this study provides a beneficial Ala127Ser mutant form of J5JGB8 chitinase that can itself be developed in to an effective bioinsecticide or may be used to enhance the potential of B. bassiana strain ARSEF 2860 bioinsecticide using enzyme engineering approach to encourage agricultural sustainability.

Nonlinear optical (NLO) materials play a crucial role in various hi-tech optoelectronic applications, driving the quest for novel molecular frameworks with superior properties. In this context, this study systematically explores derivatives of phenanthrene-carbazole and phenyleno-borole, aiming to finely tune their NLO properties by incorporating multiple push-pull groups at their molecular periphery. The integration of these push-pull groups with the central core significantly enhances intramolecular charge transfer (ICT) within the molecular structures, leading to improved optical and NLO properties. Our findings highlight compound 3-PB as a standout among the designated compounds, exhibiting exceptional linear optical properties with the maximum linear isotropic (α_iso) value of 95.77 × 10^-24 esu and a maximum anisotropic (α_aniso) of 106.6 × 10^-24 esu. Notably, it also shows an impressive average static third-order NLO polarizability <γ> amplitude of 574.1 × 10^-36 esu. A comparative study reveals that the <γ> amplitude of 3-PB is ∼78 times greater than p-NA (7.29 × 10^-36 esu) at the M06/6-311G∗∗ level of theory. TD-DFT computations further attribute the remarkable NLO response of 3-PB to its lower transition energy, setting it apart from the other designated molecular systems. Additionally, TD-DFT calculations explored structure-NLO property relations through FMOs, DOS, and MEP maps. A detailed comparison of NLO polarizabilities and electronic properties highlights the significance of carbazole and borole-based systems in achieving strong NLO responses. Notably, compound 3-PB exhibits enhanced NLO properties due to the presence of polyaromatic rings and a boron atom serving as an acceptor, along with dimethylamine (donor group) substitutions at the periphery of the molecule. Beyond exceptional NLO performance, our entitled systems also demonstrate favorable photovoltaic potential. Specifically, compound 3-PB exhibits the highest LHE value of 0.999. Additionally, open circuit voltage values range from 1.55 to 3.02 eV, while lower ΔG_reg values suggest that these compounds are promising candidates for sensitizing DSSC performance.

AMPK (AMP-activated protein kinase) is a crucial signaling protein found in essentially all eukaryotic organisms and acts as an energy sensor. When activated by metabolic stress, AMPK phosphorylates a variety of molecular targets, altering enzyme activity and gene expression to regulate cellular responses. In general, in response to low intracellular ATP levels (high ADP:ATP ratio), AMPK triggers the activation of energy-producing pathways while simultaneously inhibiting energy-consuming processes. Recent studies have established a connection between molecular pathways involved in sensing energy and potential for extending longevity. AMPK indirect activator compounds have shown a potential strategy to obtain an anti-aging biological activity. This study explores the conformational changes and transient druggable binding pockets over the 1 μs trajectory of molecular dynamics simulations to comprehend the behavior of main domains and allosteric drug and metabolite (ADaM) site. The described conformations of the apo-ADaM site suggest an important influence of specific residues on the cavity volume variations. A clustering set of representative AMPK conformations allowed to identify the more favorable binding site volume and shape at the protein apo form, including the carbohydrate-binding module (CBM) region which exhibited a stable movement near the ADaM site of the alpha-subunit. The identification of gamma-subunit transient druggable binding pocket CBS3 during the microscale time trajectory simulations also offers valuable insights into structure-based AMP-mimetic drug design for AMPK activation.