In Silico Evaluation of Oligomeric Representations for Molecularly Imprinted Polymer Modeling Using a Biological Template.

Molecularly imprinted polymers (MIPs) have significant relevance to analytical sensing due to their functionalized and template-specific structurally complementary cavities, providing increased sensibility and specificity for instrumental analyses, thereby enabling a wide variety of applications, especially for biological processes. Designing and developing MIPs entirely by experimental approaches are time-consuming and costly processes; thus, computational tools are used to assess some of the most critical parameters for imprinting, such as ligand screening. A typical practice is to model functional ligands as monomers; however, this representation fails to predict how ligand-template interactions evolve during polymer growth. In this context, this work aims to evaluate whether additional oligomeric representations affect the formation of noncovalent complexes between typical ligands and the P31 Asian lineage Zika virus epitope, using classical molecular dynamics. The ligands 2-vinylpyridine, 4-vinylaniline, acrylic acid, acrylamide, and 2-hidroxyethyl methacrylate were simulated as monomers, trimers, pentamers, and decamers, and their influence on the epitope structural conservation and ligand-template interactions were evaluated. Analyses of root-mean-square deviation, fluctuation, radius of gyration, pair correlation function, and number of hydrogen bonding-type interactions were conducted, showing the ligand chain size had an influence on the complex formation. However, this influence had no discernible pattern, exhibiting better performance in some cases while noninfluential in others. Of particular significance, in terms of epitope structural conservation, distinct oligomeric chains led to the selection of the distinct most interactive ligands. This observation raises important questions regarding the use of oligomeric chains in MIP simulations, thus prompting the need for further investigations of this subject.

Interaction of the nitrosyl ruthenium complex [RuII (NH.NHq-R)(tpy)NO]3+ with human serum albumin: a spectroscopic and computational investigation.

The interaction between two nitrosyl ruthenium complexes [Ru (NH.NHq-COOH)(tpy)NO](PF6 )3 (RuBDQ) and [Ru (NH.NHq-H)(tpy)NO](PF6 )3 (RuBD) and human serum albumin (HSA) was investigated using spectroscopic and computational methods. From fluorescence experiments, a dynamic quenching mechanism and binding constants at a single site demonstrated the higher stability of the RuBDQ-HSA system at 308 K compared with RuBD-HSA. Thermodynamic parameters indicated that binding of RuBDQ and RuBD to HSA was mainly driven by hydrophobic interaction and hydrogen bonding, respectively. Synchronous fluorescence and FT-IR results suggested that interactions between both nitrosyl ruthenium complexes and HSA affected protein conformation. Competition experiments revealed that RuBDQ and RuBD bound to Sudlow sites I and II, respectively. Molecular docking results showed that RuBDQ interacted with Ser-192 and Ala-291 residues via hydrogen bonding and polar contact, respectively, whereas RuBD associated with Asn-391 via a polar interaction. Noncovalent interaction results suggested that van der Waals interactions were the main binding forces for both systems, i.e. RuBDQ associated with Trp-214 via van der Waals interaction and with Ty-150 via dipole-dipole bonding, whereas RuBD associated with Tyr-452 via van der Waals forces. The Asp-391 residue interacted with the nitrosyl ligand via polar contact and the terpyridine ligand via van der Waals interaction.

Is a non-synonymous SNP in the HvAACT1 coding region associated with acidic soil tolerance in barley?

Abstract The barley HvAACT1 gene codes for a citrate transporter associated with tolerance to acidic soil. In this report, we describe a single nucleotide polymorphism (SNP) in the HvAACT1 coding region that was detected as T-1,198 (in genotypes with lower root growth on acidic soil) or G-1,198 (greater root growth) and resulted in a single amino acid change (L/V-172). Molecular dynamic analysis predicted that HvAACT1 proteins with L or V-172 were stable, although the substitution led to structural changes within the protein. To evaluate the effect of the SNP on tolerance to acidic soil, barley accessions were separated into haplotypes based on the presence of a 1 kb insertion in the HvAACT1 promoter and a 21 bp insertion/deletion. These markers and the SNP-1,198 allowed the identification of five haplotypes. Short-term soil experiments showed no difference in root growth for most of the accessions containing the 21 bp insertion and T or G-1,198. In contrast, genotypes showing both the 21 bp deletion and G-1,198, with one of them having the 1 kb insertion, showed greater root growth. These results indicate that the SNP was not advantageous or deleterious when genotypes from the same haplotype were compared. The occurrence of the SNP was highly correlated with the 21 bp insertion/deletion that, together with the 1 kb insertion, explained most of the barley tolerance to acidic soil.

Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca²âº-ATPase PfATP6.

Malaria is responsible for more deaths around the world than any other parasitic disease. Due to the emergence of strains that are resistant to the current chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains urgent though hampered by a lack of knowledge regarding the molecular mechanisms of artemisinin resistance. Semisynthetic compounds derived from diterpenes from the medicinal plant Wedelia paludosa were tested in silico against the Plasmodium falciparum Ca2+-ATPase, PfATP6. This protein was constructed by comparative modelling using the three-dimensional structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking scores, indicating a better interaction with PfATP6 than that of thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote a change in calcium homeostasis, leading to parasite death. These data suggest PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes.

Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca2+-ATPase PfATP6

Malaria is responsible for more deaths around the world than any other parasitic disease. Due to the emergence of strains that are resistant to the current chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains urgent though hampered by a lack of knowledge regarding the molecular mechanisms of artemisinin resistance. Semisynthetic compounds derived from diterpenes from the medicinal plant Wedelia paludosa were tested in silico against the Plasmodium falciparum Ca2+-ATPase, PfATP6. This protein was constructed by comparative modelling using the three-dimensional structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking scores, indicating a better interaction with PfATP6 than that of thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote a change in calcium homeostasis, leading to parasite death. These data suggest PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes.