Development of computational tools has improved our understanding of protein dynamics. In this review we highlight computational efforts to understand flap dynamics and conformational aspartic flexibility in aspartic proteases and their role in ligand recognition and substrate binding.

We explored a novel allosteric site of kinesin Eg5 and identified new Eg5 inhibitors using structure-based virtual screening. The identified compounds significantly induced monopolar spindle formation in colorectal cancer HCT116 cells and suppressed cancer cell viability and colony formation. Our findings reveal a new allosteric regulation mechanism of Eg5 and a novel drug targeting site for cancer therapy.

Human serum paraoxonase (hPON1) protects low-density lipoproteins against oxidative stress and prevent atherosclerosis development. Anticancer agents have cardiotoxic effects, and this situation can lead to significant complications. The aim was to evaluate the in vitro effects of some of the anticancer agents such as cetuximab, paclitaxel, etoposide, docetaxel, and ifosfamide on the activity of hPON1 in this study. These drugs reduced the activity of hPON1. Consequently, inhibition of hPON1 by these anticancer agents may explain some of the cardiotoxic actions of these drugs.

In this article, four novel substrates with long halftime have been designed and synthesized successfully for luxAB bacterial bioluminescence. After in vitro and in vivo biological evaluation, these molecules can emit obvious bioluminescence emission with known bacterial luciferase, thus indicating a new promising approach to developing the bacterial bioluminescent system.

β-lactoglobulin nanocapsules were synthesized for colon cancer oral drug delivery. The best nanocapsules were obtained at pH 4.5 in the presence of pectin. Drug release from β-LG nanocapsules is pH sensitive, and the nanocapsules are stable in acidic conditions.

We present here the computer-aided rational design and the synthesis of new small molecule TLR4 modulators: fluorescent compounds 1 and 2 and homodimers 3 and 4. These non-toxic molecules were active in inhibiting LPS-triggered TLR4 stimulus in HEK-Blue cells and molecule 1 was used as fluorescent label for LPS-binding proteins in confocal microscopy experiments on cells.

The paclitaxel-loaded sirolimus-conjugated albumin nanoparticles were prepared to enhance cytotoxicity of paclitaxel to cancer cells. The cellular studies showed that paclitaxel concentration ratio to sirolimus and time of sirolimus release after paclitaxel were two important factors in cytotoxic effects. We guess that when cancer cell lines arrest in G2-M by anticancer drugs like paclitaxel, Akt activates mTOR to make cells continue living, then inhibiting mTOR can enhance anticancer effects.

A series of novel imidazo[4,5-b]pyridin-2-ylthioacetanilides were designed, synthesized, and evaluated for their antiviral activities through combining bioisosteric replacement and structure-based drug design. Almost all of the title compounds displayed a moderate to excellent activities against wild-type (wt) HIV-1 strain with EC₅₀ values ranging from 0.059 to 1.41 μm in a cell-based antiviral assay. Preliminary structure–activity relationships (SARs) and molecular modeling studies were detailedly discussed, which may provide valuable insights for further optimization.

PTEN has been described as the most frequently mutated tumor suppressor gene in human cancer. We described here the synthesis of new H₄ receptor ligands and their interaction with the promoter of PTEN gene demonstrated by using electrophoretic mobility shift assay. Several compounds based on the well-known H₄R antagonist JNJ7777120 structure showed high effect on PTEN promoter mobility. However, no correlation between PTEN interaction and anti-neuroblastoma activity was found. Moreover, one triazine derivative with the highest H₄R affinity was shown as a promising and non-cytotoxic lead structure.

Two series of GA derivatives were synthesized and evaluated for their anti-gastric ulcer activity. The data obtained from in vivo testing of these compounds in a rodent ethanol-induced stomach injury model showed that A1, A4, and A9 (ulcer index: 1.125 ± 1.246**, 1.714 ± 0.756*, 1.875 ± 1.126*) exhibited better anti-gastric ulcer activity than the positive control Omeprazole (2.005 ± 1.011*).

Different in silico approaches were applied to study the specific interactions of non-secosteroidal ligands in VDR active site. The article summarizes the importance of similar ligand efficacy and the distinct ligand potency in the VDR active site. The results could be useful for the designing of potent agonists in the lead optimization phase of drug discovery against VDR.

The medium-chain acyl-CoA dehydrogenase (MCAD) is an enzyme that catalyzes the first step of mitochondrial fatty acid β-oxidation pathway. Herein, we analyzed the structural stability and dynamic behavior of MCAD wild-type by means of molecular dynamics studies. Our results revealed that the FAD cofactor has an important structural role on the tetramer stability and also in maintaining the volume of the catalytic pockets. We confirmed that the presence of fatty-acyl substrate changes the dynamics of the catalytic pockets favoring the reaction mechanism.

We have identified two antitubercular (anti-TB) 5-alkylresorcinols, 5-(8Z-heptadecenyl) resorcinol (1) and 5-(8Z-pentadecenyl) resorcinol (2) through bioassay-guided separation from the leaves and stems of the medicinal plant Ardisia gigantifolia, and further synthesized 15 derivatives (3-17) based on these two natural products. These compounds were evaluated for their anti-TB activity against Mycobacterium tuberculosis H₃₇R_V.

Bifunctional compound was purified and identified as Vitalboside A (VBA), exhibiting antidiabetic and anti-adipogenic activity. Biochemical and docking analysis confirms VBA as an allosteric non-competitive inhibitor of PTP1B. Inhibitor studies and Western blot analysis revealed that VBA is a potential insulin-sensitizing candidate which increases glucose transport (GLUT 4) in a PI3K/AKT-dependent manner. In silico and in vitro studies showed partial transactivation of peroxisome proliferator-activated receptor γ, with an increase in adiponectin secretion, confirming the anti-adipogenic potential of VBA.