Effects of Bacillus in Pectobacterium quorum quenching: A survey of two different acyl-homoserine lactonases.

Numerous functions in pathogenic Pectobacterium are regulated by quorum sensing (QS). Two different aiiA genes isolated from Bacillus sp. A24(aiiA) and Bacillus sp.

Reconstruction of the unbinding pathways of new inhibitors of the SARS-CoV-2 papain-like protease using molecular dynamics simulation.

Developing novel antiviral drugs against the SARS-CoV-2 virus and COVID-19 disease is imperative as the vaccines may not offer absolute protection. PLpro plays a crucial role in the viral life cycle, making it an attractive target for drug development. Several PLpro inhibitors have been developed, and their 3D structures in complex with PLpro are available.

Comparative study of the unbinding process of some HTLV-1 protease inhibitors using unbiased molecular dynamics simulations.

The HTLV-1 protease is one of the major antiviral targets to overwhelm this virus. Several research groups have developed protease inhibitors, but none has been successful. In this regard, developing new HTLV-1 protease inhibitors to fix the defects in previous inhibitors may overcome the lack of curative treatment for this oncovirus.

Reconstruction of the unbinding pathways of noncovalent SARS-CoV and SARS-CoV-2 3CLpro inhibitors using unbiased molecular dynamics simulations.

The main protease (3CLpro) is one of the essential components of the SARS-CoVs viral life cycle, which makes it an interesting target for overpowering these viruses. Although many covalent and noncovalent inhibitors have been designed to inhibit this molecular target, none have gained FDA approval as a drug. Because of the high rate of COVID-19 pandemic development, in addition to laboratory research, we require in silico methods to accelerate rational drug design.

Reconstruction of the binding pathway of an anti-HIV drug, Indinavir, in complex with the HTLV-1 protease using unaggregated unbiased molecular dynamics simulation.

Retroviruses are a growing concern for the health of human beings, and one of the dangerous members of this family is the Human T-cell Leukemia Virus 1 (HTLV-1) virus. It has affected more than 20 million people so far, and since there are no registered treatments against it yet, urgent treatment solutions are needed. One of the most promising drug targets to fight this virus is the protease enzyme of the virus's protein machinery.

Comparative analysis of the unbinding pathways of antiviral drug Indinavir from HIV and HTLV1 proteases by supervised molecular dynamics simulation.

Determining the unbinding pathways of potential small molecule compounds from their target proteins is of great significance for designing efficacious treatment solutions. One of these potential compounds is the approved HIV-1 protease inhibitor, Indinavir, which has a weak effect on the HTLV-1 protease. In this work, by employing the SuMD method, we reconstructed the unbinding pathways of Indinavir from HIV and HTLV-1 proteases to compare and understand the mechanism of the unbinding and to discover the reasons for the lack of inhibitory activity of Indinavir against the HTLV-1 protease.

Complete reconstruction of dasatinib unbinding pathway from c-Src kinase by supervised molecular dynamics simulation method; assessing efficiency and trustworthiness of the method.

Over the past years, rational drug design has gained lots of attention since employing it gave the world targeted therapy and more effective treatment solutions. Structure-based drug design (SBDD) is an excellent tool in rational drug design that takes advantage of accurate methods such as unbiased molecular dynamics (UMD) simulation for designing and optimizing molecular entities by understanding the binding and unbinding pathways of the binders. Supervised molecular dynamics (SuMD) simulation is a branch of UMD in which long-duration simulations are turned into short simulations, called replica, and a specific parameter is monitored throughout the simulation.

Unraveling the unbinding pathways of SARS-CoV-2 Papain-like proteinase known inhibitors by Supervised Molecular Dynamics simulation.

The COVID-19 disease has infected and killed countless people all over the world since its emergence at the end of 2019. No specific therapy for COVID-19 is not currently available, and urgent treatment solutions are needed. Recent studies have found several potential molecular targets, and one of the most critical proteins of the SARS-CoV-2 virus work machine is the Papain-like protease (Plpro).

A boosted unbiased molecular dynamics method for predicting ligands binding mechanisms: probing the binding pathway of dasatinib to Src-kinase.

Summary: Small molecules such as metabolites and drugs play essential roles in biological processes and pharmaceutical industry. Knowing their interactions with biomacromolecular targets demands a deep understanding of binding mechanisms. Dozens of papers have suggested that discovering of the binding event by means of conventional unbiased molecular dynamics (MD) simulation urges considerable amount of computational resources, therefore, only one who holds a cluster or a supercomputer can afford such extensive simulations.

Rational drug repurposing for cancer by inclusion of the unbiased molecular dynamics simulation in the structure-based virtual screening approach: Challenges and breakthroughs.

Managing cancer is now one of the biggest concerns of health organizations. Many strategies have been developed in drug discovery pipelines to help rectify this problem and two of the best ones are drug repurposing and computational methods. The combination of these approaches can have immense impact on the course of drug discovery.

Are zinc oxide nanoparticles safe? A structural study on human serum albumin using and methods.

With due attention to adsorption of proteins on the nanoparticles surface and the formation of nanoparticle-protein corona, investigation of nanoparticles toxicity on the structure of proteins is important. Therefore, this work was done to evaluate toxicity of Zinc oxide nanoparticles (ZnO NPs) on the structure of human serum albumin (HSA) through and studies. First, ZnO NPs were synthesized using hydrothermal method and their size and morphology were determined by SEM and TEM methods and then to study its toxicity on the HSA structure were used UV-Vis and fluorescence spectroscopy.

Prediction of novel inhibitors for l-amino acid oxidase by repurposing FDA-approved drugs: a virtual screening and molecular dynamics simulation investigation.

One of the deadliest enzymes in the snake venom is l-amino acid oxidase (LAAO) which plays an important role in the pathophysiological effects during snake envenomation. Some effects of this enzyme on the human body are apoptosis, platelet aggregation, edema, hemorrhage, and cytotoxicity. Hence, inhibiting the enzyme activity to reduce its degradation effects is of great medical and pharmacological importance.

Performing an In Silico Repurposing of Existing Drugs by Combining Virtual Screening and Molecular Dynamics Simulation.

Drug repurposing has become one of the most widely used methods that can make drug discovery more efficient and less expensive. Additionally, computational methods such as structure-based drug designing can be utilized to make drug discovery more efficient and more accurate. Now imagine what can be achieved by combining drug repurposing and computational methods together in drug discovery, "in silico repurposing.

Repurposing existing drugs for new AMPK activators as a strategy to extend lifespan: a computer-aided drug discovery study.

Dietary restriction is one of the several ways which could putatively extend organisms' lifespan, ranging from Saccharomyces cerevisiae to rodents, by activating the AMP-activated protein kinase (AMPK), an ATP/AMP sensor. Extensive researches have shown that aging reduces sensibility of AMPK and eventually causes energy imbalance in cells. Research in mammals' AMPK depicts that this signaling molecule could control autophagy, improve cellular stress resistance and suppress inflammatory responses.

Prediction of new chromene-based inhibitors of tubulin using structure-based virtual screening and molecular dynamics simulation methods.

Multidrug resistance (MDR) is one of the serious problems in cancer research that causes failure in chemotherapy. Chromene-based compounds have been proven to be the novel anti-MDR agents for inhibiting proliferation of tumor cells through tubulin polymerization inhibition of by binding at the colchicine binding site. In this study, we screened a chromene-based database of small molecules using physicochemical, ADMET properties and molecular docking to identify potential hit compounds.

In silico drug repurposing of FDA-approved drugs to predict new inhibitors for drug resistant T315I mutant and wild-type BCR-ABL1: A virtual screening and molecular dynamics study.

The BCR-ABL fusion gene is one of the major causes of 95% of Chronic Myeloid Leukemia (CML). While, BCR-ABL protein is currently being used as a major target to treat CML. Although, current FDA-approved drugs such as; Imatinib and Nilotinib have stupendously improved the patients 5-year's survival rates, the drug resistance has dramatically reduced their effects.

In vitro antitumor evaluation of 4H-chromene-3-carbonitrile derivatives as a new series of apoptotic inducers.

Apoptosis is a naturally occurring process by which a cell is directed to programmed cell death. Chemotherapy drugs affect the cancer cells by the apoptotic induction. During the present study, a series of 4H-chromene-3-carbonitrile was synthesized by one-pot method as the inducers of apoptosis.

Synthesis and biological evaluation of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones as combretastatin analogs.

A series of 3-(trimethoxyphenyl)-2(3H)-thiazole thiones 5 were designed as new heterocyclic analogs of combretastatin A-4 (CA-4). Indeed, the olefinic core structure of CA-4 has been replaced by 2(3H)-thiazole thione. The general synthetic strategy to prepare compounds 5 was based on the cyclocondensation reaction between triethylammonium N-(trimethoxyphenyl)dithiocarbamate and appropriate phenacyl halide.

Synthesis and biological evaluation of novel benzyl piperazine derivatives of 5-(5-nitroaryl)-1,3,4-thiadiazoles as Anti-Helicobacter pylori agents.

Background And The Purpose Of The Study: Helicobacter pylori is recognized as the main cause of gastritis and gastroduodenal ulcers and classified as class 1 carcinogen pathogen. Different 1,3,4-thiadiazole derivatives bearing 5-nitroaryl moiety have been shown considerable anti- H. pylori activity.

Anti-proliferative and apoptotic effects of the derivatives from 4-aryl-4H-chromene family on human leukemia K562 cells.

Previous studies suggest that 4-aryl-4H-chromenes are potent apoptosis-inducing agents in various cancer cell lines. In this study, anti-proliferative and apoptotic effects of the derivatives from 4-aryl-4H-chromene family were investigated in the human leukemia K562 cells using [3-(4,5)-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) growth inhibition assay. 3-NC was more active among these compounds with IC₅₀ of 65 nM and was selected for further studies.

Altered tubulin assembly dynamics with N-homocysteinylated human 4R/1N tau in vitro.

Tau isoforms promote neuronal integrity through binding and stabilization of microtubule proteins (MTP). It has been shown that hyperphosphorylation of tau contributes to Alzheimer's disease (AD) pathology and related tauopathies. However, other pathogenic modifications of tau have not been well characterized.

Induction of apoptosis through tubulin inhibition in human cancer cells by new chromene-based chalcones.

Context: As microtubules are highly involved in cellular growth, it appears to be a preferential target for cancer treatment. Therefore, many efforts have been performed to discover drugs that affect on microtubule function. Several microtubule inhibitors are in various stages of laboratory evaluations and clinical trials.

Effect of N-homocysteinylation on physicochemical and cytotoxic properties of amyloid β-peptide.

Abstract Hyperhomocysteinemia has recently been identified as an important risk factor for Alzheimer's disease (AD). One of the potential mechanisms underlying harmful effects of homocysteine (Hcy) is site-specific acylation of proteins at lysine residues by homocysteine thiolactone (HCTL). The accumulation of amyloid β-peptide (Aβ) in the brain is a neuropathological hallmark of AD.