Nanosecond molecular dynamics using the Ewald summation method have been performed to elucidate the structural and energetic role of the closing base pair in loop–loop RNA duplexes neutralized by Mg2+ counterions in aqueous phases. Mismatches GA, CU and Watson–Crick GC base pairs have been considered for closing the loop of an RNA in complementary interaction with HIV-1 TAR. The simulations reveal that the mismatch GA base, mediated by a water molecule, leads to a complex that presents the best compromise between flexibility and energetic contributions. The mismatch CU base pair, in spite of the presence of an inserted water molecule, is too short to achieve a tight interaction at the closing-loop junction and seems to force TAR to reorganize upon binding. An energetic analysis has allowed us to quantify the strength of the interactions of the closing and the loop–loop pairs throughout the simulations. Although the water-mediated GA closing base pair presents an interaction energy similar to that found on fully geometry-optimized structure, the water-mediated CU closing base pair energy interaction reaches less than half the optimal value. 相似文献
We study the binding of the neutral Agn (n = 8, 10, 12) to the DNA base-adenine (A), guanine (G) and Watson–Crick –adenine-thymine, guanine-cytosine pairs. Geometries of complexes were optimized at the DFT level using the hybrid B3LYP functional. LANL2DZ effective core potential was used for silver and 6–31 + G** was used for all other atoms. NBO charges were analyzed using the Natural population analysis. The absorption properties of Agn–A,G/WC complexes were also studied using time-dependent density functional theory. The absorption spectra for these complexes show wavelength in the visible region. It was revealed that silver clusters interact more strongly with WC pairs than with isolated DNA complexes. Furthermore, it was found that the electronic charge transferred from silver to isolated DNA clusters are less than the electronic charge transferred from silver to the Agn–WC complexes. The vertical ionization potential, vertical electron affinity, hardness, and electrophilicity index of Agn–DNA/WC complexes have also been discussed. 相似文献
The cold shock protein from the hyperthermophile Thermotoga maritima (Tm-Csp) exhibits significantly higher thermostability than its homologue from the thermophile Bacillus caldolyticus (Bc-Csp). Experimental studies have shown that the electrostatic interactions unique to Tm-Csp are responsible for improving its thermostability. In the present work, the favorable charged residues in Tm-Csp were grafted into Bc-Csp by a double point mutation of S48E/N62H, and the impacts of the mutation on the thermostability and unfolding/folding behavior of Bc-Csp were then investigated by using a modified Gō model, in which the electrostatic interactions between charged residues were considered in the model. Our simulation results show that this Tm-Csp-like charged residue mutation can effectively improve the thermostability of Bc-Csp without changing its two-state folding mechanism. Besides that, we also studied the unfolding kinetics and unfolding/folding pathway of the wild-type Bc-Csp and its mutant. It is found that this charged residue mutation obviously enhanced the stability of the C-terminal region of Bc-Csp, which decreases the unfolding rate and changes the unfolding/folding pathway of the protein. Our studies indicate that the thermostability, unfolding kinetics and unfolding/folding pathway of Bc-Csp can be artificially changed by introducing Tm-Csp-like favorable electrostatic interactions into Bc-Csp.
