Experimental and theoretical insights for designing Zn2+ complexes to trigger chemo-selective hetero-coupling of alcohols.

Designing well-defined Zn-complexes for sustainable dehydrogenative catalysis overcoming the difficulties associated with activating Zn2+(d10)-metal species is considered paramount goal in catalysis. Herein, we explore the plausibility of ß-alkylation of secondary alcohols with primary alcohols by well-defined 3d10 Zn-complexes. Detailed organometallic and catalytic investigations, in conjunction with computational analyses, were conducted to ascertain the potential involvement of the catalyst at various stages of the catalytic process.

Stability of trimeric DENV envelope protein at low and neutral pH: an insight from MD study.

Change in pH plays a crucial role in the stability and function of the dengue envelope (DENV) protein during conformational transition from dimeric (pre-fusion state) to trimeric form (post-fusion state). In the present study we have performed various molecular dynamics (MD) simulations of the trimeric DENV protein at different pH and ionic concentrations. We have used total binding energy to justify the stability of the complex using the MMPBSA method. We found a remarkable increase in the stability of the complex at neutral pH (pH~7) due to the increment of sodium ions. However, at very low pH (pH~4), the total energy of the complex becomes high enough to destabilize the complex. At a specific pH, almost at a range of 6, the stability of the complex is significantly better than the stability of the trimer at neutral pH, which connotes that the trimer is most stable at this pH (pH~6).

Stability and free energy calculation of LNA modified quadruplex: a molecular dynamics study.

Telomeric ends of chromosomes, which comprise noncoding repeat sequences of guanine-rich DNA, which are the fundamental in protecting the cell from recombination and degradation. Telomeric DNA sequences can form four stranded quadruplex structures, which are involved in the structure of telomere ends. The formation and stabilization of telomeric quadruplexes has been shown to inhibit the activity of telomerase, thus establishing telomeric DNA quadrulex as an attractive target for cancer therapeutic intervention. Molecular dynamic simulation offers the prospects of detailed description of the dynamical structure with ion and water at molecular level. In this work we have taken a oligomeric part of human telomeric DNA, d(TAGGGT) to form different monomeric quadruplex structures d(TAGGGT)4. Here we report the relative stabilities of these structures under K⁺ ion conditions and binding interaction between the strands, as determined by molecular dynamic simulations followed by energy calculation. We have taken locked nucleic acid (LNA) in this study. The free energy molecular mechanics Poission Boltzman surface area calculations are performed for the determination of most stable complex structure between all modified structures. We calculated binding free energy for the combination of different strands as the ligand and receptor for all structures. The energetic study shows that, a mixed hybrid type quadruplex conformation in which two parallel strands are bind with other two antiparallel strands, are more stable than other conformations. The possible mechanism for the inhibition of the cancerous growth has been discussed. Such studies may be helpful for the rational drug designing.

Role of pH on dimeric interactions for DENV envelope protein: an insight from molecular dynamics study.

The entry of dengue viruses is mediated by pH triggering in the host cells. Here we have studied the DENV E protein stability and binding of its units at low and normal pH using MD and MM-PB/SA method for the first time. To investigate the role of pH in dissociation of dimeric protein, we have performed a concise study of hydrogen bonding and other interactions between units of dimer at low and normal pH. The Generalized Born calculation connotes that dimeric unit was relatively less stable and less proned for dimerisation at low pH. Our results provide a theoretical verification for previous assumptions of pH triggering mechanism of dengue envelope protein. During the pH alteration, we found a large decrement in salt bridges which were observed at normal pH. We also compared the flexibility of each unit and found that they exhibit different fluctuations during molecular dynamics simulations.