Mineralocorticoid Receptor in Endothelial Cells Contributes to Vascular Endothelial Growth Factor Receptor Inhibitor-Induced Vascular and Kidney Damage.

Background: Vascular endothelial growth factor receptor inhibitors (VEGFRis) improve cancer patient survival by inhibiting tumor angiogenesis. However, VEGFRis induce treatment-limiting hypertension which has been associated with impaired vascular endothelial cell (EC) function and kidney damage. The mineralocorticoid receptor (MR) regulates blood pressure (BP) via its effects on the vasculature and the kidney.

Inhibitory mechanism of n-MTAB AuNPs for α-synuclein aggregation.

Objective: The aggregation of alpha-synuclein (α-syn) is closely related to the pathogenesis and dysfunction of Parkinson's disease.

Methods: To investigate the potential of nanoparticlemediated therapy, the interactive mechanism between α-syn and n-myristyltrimethylammonium bromide (MTAB) Gold nanoparticles (AuNPs) with different diameters was explored by molecular dynamics simulations.

Results: The results indicated that there was a directional interaction between α-syn and n-MTAB AuNPs, in which the driving force for the binding of the C-terminus in α-syn came from electrostatic interactions and the nonamyloid β component (NAC) domain exhibited weak hydrophobic interactions as well as electrostatic interaction, thereby preventing α-syn aggregation.

Biological effect of black phosphorus nanosheets on the interaction between SARS-CoV-2 S protein and ACE2.

The binding of the spike glycoprotein (S protein) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to angiotensin-converting enzyme 2 (ACE2) is the main pathway that leads to serious coronavirus disease 2019 (COVID-19) infection. In the biomedical applications of various nanomaterials, black phosphorus nanosheets (BP) have been receiving increasing attention owing to their excellent characteristics. In this study, the biological effect of BP on the interaction between the S protein and ACE2 was investigated by molecular dynamics simulations.

Selective inhibition mechanism of nitroxoline to the BET family: Insight from molecular simulations.

Although the proteins in bromodomain and extra-terminal domain (BET) family are promising therapy drug targets for numerous human diseases, the binding effectiveness is interfered by the competition from non-BET protein BRD9. In this study, molecular docking, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition methods were employed to clarify the selective inhibition mechanism of nitroxoline. The results showed that the different cavity volume of effective embedding inhibitor and the changes in conserved residues were associated with the significant higher selectivity of inhibitor nitroxoline for BET family than non-BET protein (BRD9).

Study of the controversial resveratrol that interact with the endogenous glutathione thiyl radical in cancer cells.

Found in various natural food products, many evidence indicated that resveratrol (RES) has been linked to neuroprotective and cardioprotective effects and prevent cancer development. However, human clinical trials have been conducted with varying results, making the usage of RES controversial. In this paper, we demonstrated that the drug RES could be conjugated with the high levels of endogenous GS in cancer cells.

One-pot facile synthesis of CuNCs/RGO nanocomposite for the sensitive detection of heparin in human serum samples.

A simple and facile one-pot approach for the synthesis of copper nanoclusters decorated reduced graphene oxide (CuNCs/RGO) nanocomposite was proposed, in which the CuNCs attached to the surface of the reduced glutathione (GSH) functionalized RGO through ligand exchange via their thiol functionalities. The synthesized nanocomposite was verified by structural characterizations, and the further investigation of density functional theory (DFT) indicated that CuR cluster (R = CHONS) with the lowest energy was the most stable structure in GSH-capped CuNCs. Although the CuNCs/RGO nanocomposite exhibited rather weak fluorescence, with the addition of heparin (Hep), the significant enhancement of fluorescence at 595 nm was achieved, which was developed to detect Hep in human serum samples with high selectivity and sensitivity.

The binding mechanism of nitroreductase fluorescent probe: Active pocket deformation and intramolecular hydrogen bonds.

Nitroreductase (NTR), a member of the flavoenzyme family, could react with nicotinamide adenine dinucleotide by reducing nitro to amino at hypoxic tumor, which can be monitored by some fluorescent probes in vivo. Here, molecular docking and molecular dynamics simulation techniques were used to explore the molecular mechanisms between NTR and probes. The results showed that formation of hydrogen bond in 1F5V-13 between A@His215 and B@Ser41 with 74.

Study on Biocompatibility of AuNPs and Theoretical Design of a Multi-CDR-Functional Nanobody.

The investigation on proteinlike specific functions of nanoparticles (NPs) has been a huge challenge. Here, the biocompatibility of Au nanoparticles (AuNPs) to antigens hen egg white lysozyme and epidermal growth factor receptor was studied first by molecular dynamics (MD) simulations and the research results revealed that antigens could form quickly a stable binding with the AuNPs and kept the structural integrity of the protein, which demonstrated better biocompatibility of AuNPs. Then, two types of complementary-determining regions (CDRs) were grafted onto the AuNPs to design a novel multi-CDR-functional nanobody.

Molecular mechanisms of tetrahydropyrrolo[1,2-c]pyrimidines as HBV capsid assembly inhibitors.

As an attractive therapeutic strategy for chronic hepatitis B virus (HBV), HBV capsid assembly inhibitors have got increased attention, which induce aberrant capsid assembly and thereby affect viral replication. In this work, molecular docking, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition were implemented to investigate the binding mechanism between tetrahydropyrrolopyrimidines scaffold inhibitors and HBV capsid protein. The obtained results displayed that the non-polar interaction, hydrogen bond interaction, polar interaction and π-π stacking interaction together help to stabilize the conformation of inhibitors in the interface of HBV core proteins, and residues Pro25, Thr33, Trp102, Ile105, Tyr118, Ile139, Leu140 (chain B), and Val124, Trp125, Thr128, Arg133 (chain C) were important participants during binding process.

Molecular inhibitory mechanism study on the potent inhibitor brigatinib against four crizotinib-resistant ALK mutations.

As a potent and selective drug, brigatinib exhibits high efficacy against wild-type and mutant anaplastic lymphoma kinase (ALK) proteins to treat non-small cell lung cancer. In this work, the mechanisms of brigatinib binding to wild type and four mutant ALKs were investigated to gain insight into the dynamic energetic and structural information with respect to the design of novel inhibitors. Comparison between ALK-brigatinib and ALK-crizotinib suggests that the scaffold of brigatinib is well anchored to the residue Met1199 of hinge region by two hydrogen bonds, and the residue Lys1150 has the strong electrostatic interaction with the dimethylphosphine oxide moiety in brigatinib.

Molecular mechanism study of several inhibitors binding to BRD9 bromodomain based on molecular simulations.

Bromodomain-containing protein 9 (BRD9) has been employed as a potential target for anticancer drugs in recent years. In this work, molecular docking, molecular dynamics (MD) simulations, binding free energy calculations, and per residue energy decomposition approaches were performed to elucidate the different binding modes between four pyridinone-like scaffold inhibitors and BRD9 bromodomain. Analysis results indicate that non-polar contribution mainly deriving from van der Waals energy is a critical impact on binding affinity of inhibitors against BRD9.