Presence of EGF ligand restricts the binding ability of EgB4 nanobody to EGFR extracellular domain.

EgB4 is a nanobody that could facilitate the development of drug-nanobody conjugates or drug delivery in cancer treatment due to its specific binding ability to the EGFR transmembrane protein. More significantly, EgB4 does not hamper the EGFR function and associates with EGFR in both the presence and absence of an EGF ligand. However, the difference in EgB4-EGFR interaction with and without EGF ligand is not clear.

Assessment of potentially toxic and rare earth elements in surface soils of Dong Nai, Vietnam.

This study investigates the quantities of Rare Earth Elements (REEs) and Potentially Toxic Elements (PTEs) in Dong Nai Province's surface soils. Atomic Absorption Spectrometry (AAS) and Instrumental Neutron Activation Analysis (INAA) were used to determine element concentrations. To validate the concentration results, established reference materials (NIST 2711 and IAEA Soil-7) were used.

Imidazole[1,5-a]pyridine derivatives as EGFR tyrosine kinase inhibitors unraveled by umbrella sampling and steered molecular dynamics simulations.

Although the use of the tyrosine kinase inhibitors (TKIs) has been proved that it can save live in a cancer treatment, the currently used drugs bring in many undesirable side-effects. Therefore, the search for new drugs and an evaluation of their efficiency are intensively carried out. Recently, a series of eighteen imidazole[1,5-a]pyridine derivatives were synthetized by us, and preliminary analyses pointed out their potential to be an important platform for pharmaceutical development owing to their promising actions as anticancer agents and enzyme (kinase, HIV-protease,…) inhibitors.

Treatment of flexibility of protein backbone in simulations of protein-ligand interactions using steered molecular dynamics.

To ensure that an external force can break the interaction between a protein and a ligand, the steered molecular dynamics simulation requires a harmonic restrained potential applied to the protein backbone. A usual practice is that all or a certain number of protein's heavy atoms or Cα atoms are fixed, being restrained by a small force. This present study reveals that while fixing both either all heavy atoms and or all Cα atoms is not a good approach, while fixing a too small number of few atoms sometimes cannot prevent the protein from rotating under the influence of the bulk water layer, and the pulled molecule may smack into the wall of the active site.

Novel design of amine and metal hydroxide functional group modified onto sludge biochar for arsenic removal.

This study involved novel-designed sludge biochar (SB) adsorbed for arsenic removal with lower operating costs and higher adsorption efficiency properties. Generally, biochar only relies on micropores for pollutant adsorption, but physical adsorption is not highly efficient for arsenic removal. Therefore, in order to improve the removal efficiency of arsenic by SB, diethylenetriamine (DETA) and FeCl were used in this study to modify the surface of SB by an immersion method.

Dependence of Work on the Pulling Speed in Mechanical Ligand Unbinding.

In single-molecule force spectroscopy, the rupture force required for mechanical unfolding of a biomolecule or for pulling a ligand out of a binding site depends on the pulling speed and, in the linear Bell-Evans regime, ∼ ln(). Recently, it has been found that non-equilibrium work is better than in describing relative ligand binding affinity, but the dependence of on remains unknown. In this paper, we developed an analytical theory showing that in the linear regime, ∼ ln() + ln(), where and are constants.

Remdesivir Strongly Binds to Both RNA-Dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations.

The outbreak of a new coronavirus SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) has caused a global COVID-19 (coronavirus disease 2019) pandemic, resulting in millions of infections and thousands of deaths around the world. There is currently no drug or vaccine for COVID-19, but it has been revealed that some commercially available drugs are promising, at least for treating symptoms. Among them, remdesivir, which can block the activity of RNA-dependent RNA polymerase (RdRp) in old SARS-CoV and MERS-CoV viruses, has been prescribed to COVID-19 patients in many countries.

How Good is Jarzynski's Equality for Computer-Aided Drug Design?

Accurate determination of the binding affinity of the ligand to the receptor remains a difficult problem in computer-aided drug design. Here, we study and compare the efficiency of Jarzynski's equality (JE) combined with steered molecular dynamics and the linear interaction energy (LIE) method by assessing the binding affinity of 23 small compounds to six receptors, including β-lactamase, thrombin, factor Xa, HIV-1 protease (HIV), myeloid cell leukemia-1, and cyclin-dependent kinase 2 proteins. It was shown that Jarzynski's nonequilibrium binding free energy Δ correlates with the available experimental data with the correlation levels = 0.

Probing the Binding Affinity by Jarzynski's Nonequilibrium Binding Free Energy and Rupture Time.

Binding affinity of a small ligand to a receptor is the important quantity in drug design, and it might be characterized by different quantities. The most popular one is the binding free energy, which can be estimated by several methods in conventional molecular dynamics simulation. So far in steered molecular dynamics (SMD), one can use either the rupture force or nonequilibrium pulling work as a measure for binding affinity.

EGCG inhibits the oligomerization of amyloid beta (16-22) hexamer: Theoretical studies.

An extensive replica exchange molecular dynamics (REMD) simulation was performed to investigate the progress patterns of the inhibition of (-)-epigallocatechin-3-gallate (EGCG) on the Aβ hexamer. Structural variations of the oligomers without and with EGCG were monitored and analyzed in detail. It has been found that EGCG prevents the formation of Aβ oligomer through two different ways by either accelerating the Aβ oligomerization or reducing the β-content of the hexamer.

Replica exchange molecular dynamics study of the truncated amyloid beta (11-40) trimer in solution.

Amyloid beta (Aβ) oligomers are neurotoxic compounds that destroy the brain of Alzheimer's disease patients. Recent studies indicated that the trimer is one of the most cytotoxic forms of low molecular weight Aβ oligomers. As there was limited information about the structure of the Aβ trimer, either by experiment or by computation, we determined in this work the structure of the 3Aβ oligomer for the first time using the temperature replica exchange molecular dynamics simulations in the presence of an explicit solvent.