A computational exploration into the structure, antioxidant capacity, toxicity and drug-like activity of the anthocyanidin "Petunidin".

A computational investigation on the structure and antioxidant property of a natural food colorant Petunidin (PT) was performed under DFT/B3LYP/6-31+ G (d, p). PT has a drug score of +0.804 which indicates its drug-like nature. The antioxidant property of PT was well explained by HAT mechanism and it has been found that the electron releasing substituents decreases the BDE value. PT has lowest BDE value at C3 position and is confirmed by the lowest pKa value, high atomic charge and lowest bond order. PT easily donates the hydrogen atom and exists in the deprotonated form in blood as the pKa value at C3 is less than the pH value of blood. PT shows no violation to Lipinski's rule of 5 indicating its nature as an orally admissible drug. More over PT has considerable bioactivity against nuclear receptor ligand while it shows only moderate activity towards GPCR and ion channel modulator. Also it shows moderate activity as an enzyme inhibitor and protease inhibitor but shows considerable activity as a kinase inhibitor. PT is non toxic in nature and all these factors favor its use as a potential antioxidant and a drug.

DNA interaction with RNase A alters protein conformation.

DNA-RNase H adducts were used for site specific cleavage of RNA and DNA-RNA duplexes, whereas nonspecific DNA interaction with ribonuclease A (RNase A) has been observed. The aim of this study was to examine the complexation of calf-thymus DNA with RNase A at physiological condition, using constant DNA concentration (12.5 mM) and various protein contents (1 microM to 270 microM). FTIR, UV-visible, and CD spectroscopic methods were used to analyse protein binding mode, the binding constant and the effects of nucleic acid-enzyme interaction on both DNA and protein conformations. Our structural analysis showed a strong RNase-PO2 binding and minor interaction with G-C bases with overall binding constant of K = 6.1 x 10(4) M(-1). The RNase-DNA interaction alters the protein secondary structure with a major reduction of the alpha-helix and increase of the beta-sheet and random structure, while DNA remains in the B-family structure.

Retinol and retinoic acid bind human serum albumin: stability and structural features.

Vitamin A components, retinol and retinoic acid, are fat-soluble micronutrients and critical for many biological processes, including vision, reproduction, growth, and regulation of cell proliferation and differentiation. The cellular uptake of Vitamin A is through specific interaction of a plasma membrane receptor with serum retinol-binding protein. Human serum albumin (HSA), as a transport protein, is the major target of several micronutrients in vivo. The aim of present study was to examine the interaction of retinol and retinoic acid with human serum albumin in aqueous solution at physiological conditions using constant protein concentration and various retinoid contents. FTIR, UV-vis, CD and fluorescence spectroscopic methods were used to determine retinoid binding mode, the binding constant and the effects of complexation on protein secondary structure. Structural analysis showed that retinol and retinoic acid bind non-specifically (H-bonding) via protein polar groups with binding constants of K(ret)=1.32 (+/-0.30)x10(5)M(-1) and K(retac)=3.33 (+/-0.35)x10(5)M(-1). The protein secondary structure showed no alterations at low retinoid concentrations (0.125 mM), whereas at high retinoid content (1mM), an increase of alpha-helix from 55% (free HSA) to 60% and a decrease of beta-sheet from 22% (free HSA) to 18% occurred in the retinoid-HSA complexes. The results point to a partial stabilization of protein secondary structure at high retinoid content.

Aspirin interaction with ribonuclease A.

Aspirin is an anti-inflammatory drug and a main source of protein acetylation that can alter enzymatic activity and protein functions. Ribonuclease A (RNase A) with several high-affinity binding sites is a possible target for many organic and inorganic molecules (Leonidas at al., [2003] Protein Sci. 12, 2559-2574). This study was designed to examine the interaction of aspirin with RNase Aat physiologic conditions. Reaction mixtures of constant protein concentration (3 mM) and different aspirin contents (0.0002-2 mM) are studied by ultraviolet-visible, Fourier transform infrared, and circular dichroism spectroscopic methods to determine the drug binding mode, the drug-binding constant, and the effects of drug complexation on the protein conformation in aqueous solution. Spectroscopic results showed one major binding for the aspirin-RNase complexes with overall binding constant of K = 3.57 x 10(4) M-1. Minor reductions in the protein alpha-helix from 15.5 to 14.1% (circular dichroism) using CDPro program and 26 to 21% (infrared) were observed on aspirin interaction. The changes are indicative of some degree of protein unfolding on drug complexation.

RNase A - tRNA binding alters protein conformation.

Bovine pancreatic ribonuclease A (RNase A) catalyzes the cleavage of P-O5' bonds in RNA on the 3' side of pyrimidine to form cyclic 2',5'-phosphates. Even though extensive structural information is available on RNase A complexes with mononucleotides and oligonucleotides, the interaction of RNase A with tRNA has not been fully investigated. We report the complexation of tRNA with RNase A in aqueous solution under physiological conditions, using a constant RNA concentration and various amounts of RNase A. Fourier transform infrared, UV-visible, and circular dichroism spectroscopic methods were used to determine the RNase binding mode, binding constant, sequence preference, and biopolymer secondary structural changes in the RNase-tRNA complexes. Spectroscopic results showed 2 major binding sites for RNase A on tRNA, with an overall binding constant of K = 4.0 x 105 (mol/L)-1. The 2 binding sites were located at the G-C base pairs and the backbone PO2 group. Protein-RNA interaction alters RNase secondary structure, with a major reduction in alpha helix and beta sheets and an increase in the turn and random coil structures, while tRNA remains in the A conformation upon protein interaction. No tRNA digestion was observed upon RNase A complexation.

The effects of poly(ethylene glycol) on the solution structure of human serum albumin.

Protein physical and chemical properties can be altered by polymer interaction. The presence of several high affinity binding sites on human serum albumin (HSA) makes it a possible target for many organic and polymer molecules. This study was designed to examine the interaction of HSA with poly(ethylene glycol) (PEG) in aqueous solution at physiological conditions. Fourier transform infrared, ultraviolet-visible, and CD spectroscopic methods were used to determine the polymer binding mode, the binding constant, and the effects of polymer complexation on protein secondary structure. The spectroscopic results showed that PEG is located along the polypeptide chains through H-bonding interactions with an overall affinity constant of K = 4.12 x 10(5) M(-1). The protein secondary structure showed no alterations at low PEG concentration (0.1 mM), whereas at high polymer content (1 mM), a reduction of alpha-helix from 59 (free HSA) to 53% and an increase of beta-turn from 11 (free HSA) to 22% occurred in the PEG-HSA complexes (infrared data). The CDSSTR program (CD data) also showed no major alterations of the protein secondary structure at low PEG concentrations (0.1 and 0.5 mM), while at high polymer content (1 mM), a major reduction of alpha-helix from 69 (free HSA) to 58% and an increase of beta-turn from 7 (free HSA) to 18% was observed.