Search results for " DOCKING"
showing 10 items of 226 documents
Corylus avellana: A Source of Diarylheptanoids With α-Glucosidase Inhibitory Activity Evaluated by in vitro and in silico Studies
2022
Corylus avellana hard shells, green leafy involucres, leaves, and male flowers have shown to be a source of diarylheptanoids, a class of natural products with promising biological activities. Cyclic diarylheptanoids, named giffonins, were isolated from the Italian cultivar “Tonda di Giffoni.” Even if many efforts have been made to establish the chemistry of these compounds, little is known about their biological properties. Herein, the inhibitory effects of diarylheptanoids isolated from C. avellana byproducts against α-glucosidase enzyme were evaluated. Molecular docking experiments disclosed the establishment of several key interactions between all the screened diarylheptanoids and the pr…
Study of the aryl hydrocarbon receptor mediated effects through in silico modeling and in vitro bioassays
2020
The aryl hydrocarbon receptor (AhR) is a cytoplasmatic sensor of diverse endogenous and exogenous substances. In a toxicological context, the former known as “dioxin receptor” has been investigated as a xenobiotic chemoreceptor and due to its roles in mediating carcinogenesis, endocrine disruption, among other immunological, hepatic, cardiovascular, and dermal toxicity mechanisms. The deep physiological implications of AhR in cellular proliferation, adhesion, division, differentiation, as well as in the reproductive, immunological and cardiovascular homeostasis have opened a new field of research in order to harness AhR’s pharmacological potential. Hence, AhR has become a therapeutic target…
A Practical Perspective : The Effect of Ligand Conformers on the Negative Image-Based Screening
2019
Negative image-based (NIB) screening is a rigid molecular docking methodology that can also be employed in docking rescoring. During the NIB screening, a negative image is generated based on the target protein’s ligand-binding cavity by inverting its shape and electrostatics. The resulting NIB model is a drug-like entity or pseudo-ligand that is compared directly against ligand 3D conformers, as is done with a template compound in the ligand-based screening. This cavity-based rigid docking has been demonstrated to work with genuine drug targets in both benchmark testing and drug candidate/lead discovery. Firstly, the study explores in-depth the applicability of different ligand 3D conformer…
HSV-1 Glycoprotein D and Its Surface Receptors: Evaluation of Protein–Protein Interaction and Targeting by Triazole-Based Compounds through In Silico…
2023
Protein–protein interactions (PPI) represent attractive targets for drug design. Thus, aiming at a deeper insight into the HSV-1 envelope glycoprotein D (gD), protein–protein docking and dynamic simulations of gD-HVEM and gD-Nectin-1 complexes were performed. The most stable complexes and the pivotal key residues useful for gD to anchor human receptors were identified and used as starting points for a structure-based virtual screening on a library of both synthetic and designed 1,2,3-triazole-based compounds. Their binding properties versus gD interface with HVEM and Nectin-1 along with their structure-activity relationships (SARs) were evaluated. Four [1,2,3]triazolo[4,5-b]pyridines were i…
Optimizing the SYBR green related cyanine dye structure to aim for brighter nucleic acid visualization
2022
In recent years, the studies of RNA and its use for the development of RNA based vaccines have increased drastically. Although cyanine dyes are commonly used probes for studying nucleic acids, in a wide range of applications, there is still a growing need for better and brighter dyes. To meet this demand, we have systematically studied the structure of SYBR green-related cyanine dyes to gain a deeper understanding of their interactions with biomolecules especially how they interact with nucleic acids and the structural components which makes them strongly fluorescent. Herein, five new dyes were synthesized, and their photophysical properties were evaluated. Observations of photophysical cha…
Genome-Wide Inhibition of Pro-atherogenic Gene Expression by Multi-STAT Targeting Compounds as a Novel Treatment Strategy of CVDs.
2018
Cardiovascular diseases (CVDs), including atherosclerosis, are globally the leading cause of death. Key factors contributing to onset and progression of atherosclerosis include the pro-inflammatory cytokines Interferon (IFN)a and IFN? and the Pattern Recognition Receptor (PRR) Toll-like receptor 4 (TLR4). Together, they trigger activation of Signal Transducer and Activator of Transcription (STAT)s. Searches for compounds targeting the pTyr-SH2 interaction area of STAT3, yielded many small molecules, including STATTIC and STX-0119. However, many of these inhibitors do not seem STAT3-specific. We hypothesized that multi-STAT-inhibitors that simultaneously block STAT1, STAT2, and STAT3 activit…
Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti-inflammatory activity.
2019
The synthesis of inhibitors of SphK2 with novel structural scaffolds is reported. These compounds were designed from a molecular modeling study, in which the molecular interactions stabilizing the different complexes were taken into account. Particularly interesting is that 7‐bromo‐2‐(2‐phenylethyl)‐2,3,4,5‐tetrahydro‐1,4‐epoxynaphtho[1,2‐b]azepine, which is a selective inhibitor of SphK2, does not exert any cytotoxic effects and has a potent anti‐inflammatory effect. It was found to inhibit mononuclear cell adhesion to the dysfunctional endothelium with minimal impact on neutrophil–endothelial cell interactions. The information obtained from our theoretical and experimental study can be us…
OFD1mutations in males: phenotypic spectrum and ciliary basal body docking impairment
2012
Case-specific performance of MM-PBSA, MM-GBSA, and SIE in virtual screening.
2015
In drug discovery the reliable prediction of binding free energies is of crucial importance. Methods that combine molecular mechanics force fields with continuum solvent models have become popular because of their high accuracy and relatively good computational efficiency. In this research we studied the performance of molecular mechanics generalized Born surface area (MM-GBSA), molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), and solvated interaction energy (SIE) both in their virtual screening efficiency and their ability to predict experimentally determined binding affinities for five different protein targets. The protein-ligand complexes were derived with two different app…