Equilibrium constants, together with kinetic rate constants of binding, are key factors in the efficacy and safety of drug compounds, informing drug design. However, the association pathways of protein-ligand binding, which contribute to their kinetic behaviors, are little understood. In this work, we used unbiased all-atom molecular dynamics (MD) simulations with an explicit solvent model to s...

The main factors affecting the accurate and precise determination of U using ICP-MS are instrumental background, the isobaric interference of UH molecular ion on U analyte ions, and the presence of U and U peak tails. An optimized analytical method for attenuating the influence of these factors on uranium isotope ratio measurements at ultratrace level of environmental samples has been developed...

The process of moving hydrophobic amino acids into the core of a protein by desolvation is important in protein folding. However, a rapid and forced desolvation can lead to precipitation of proteins. Desolvation of proteins under controlled conditions generates nanoparticles - homogeneous aggregates with a narrow size distribution. The protein nanoparticles, under physiological conditions, unde...

The enzyme Δ(1)-pyrroline-5-carboxylate (P5C) dehydrogenase (aka P5CDH and ALDH4A1) is an aldehyde dehydrogenase that catalyzes the oxidation of γ-glutamate semialdehyde to l-glutamate. The crystal structures of mouse P5CDH complexed with glutarate, succinate, malonate, glyoxylate, and acetate are reported. The structures are used to build a structure-activity relationship that describes the se...

Two viral proteins, HIV-1 protease and HIV-1 integrase, have been targeted for inhibitor design to prevent assembly and maturation of HIV-1 virions. The enzymatic mechanism of these proteins involves side-chain groups that serve as general acids or bases. Furthermore, catalytic activity requires that water be removed from the microenvironment surrounding the chemical reaction site or be constra...

Voltage-gated ion channels open and close, or "gate," in response to changes in membrane potential. The electric field across the membrane-protein complex exerts forces on charged residues driving the channel into different functional conformations as the membrane potential changes. To act with the greatest sensitivity, charged residues must be positioned at key locations within or near the tra...

Antifungals have always been considered as one of the astonishing discoveries of the 20th century. This is correct, but the real marvel is the development of antifungal resistance in hospitals, communities, and the environment concomitant with their use. Fungal infections have emerged as an important clinical threat, with significant associated morbidity and mortality.  This study is desig...

The native ensemble of caspases is described globally by a complex energy landscape where the binding of substrate selects for the active conformation, whereas targeting an allosteric site in the dimer interface selects an inactive conformation that contains disordered active-site loops. Mutations and posttranslational modifications stabilize high-energy inactive conformations, with mostly form...

diet can play a vital role in cancer prevention. nowadays the scientists are looking for food materials which can potentially prevent the cancer occurrence. the purpose of this research is to examine anti-mutagenic and apoptotic effects of apigenin in human lymphoma cells. in present study human chronic lymphocytic leukemia (eheb cell line) were cultured in rpmi 1640 (sigma), supplemented with ...