A series of atomistic molecular dynamics (MD) simulations were carried out with a hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer with the variation of glucose concentrations from 0 to 30 wt % in the presence of 0.3 M NaCl. The study suggested that although the thickness of the lipid bilayer dropped significantly with the increase in glucose concentration, it expanded laterally at high glucose levels due to the intercalation of glucose between the headgroups of adjacent lipids. We adopted the surface assessment via the grid evaluation method to compute the deviation of the bilayer's key structural features for the different amounts of glucose present. This suggested that the accumulation of glucose molecules near the headgroups influences the local lipid bilayer undulation and crimping of the lipid tails. We find that the area compressibility modulus increases with the glucose level, causing enhanced bilayer rigidity arising from the slow lateral diffusion of lipids. The restricted lipid motion at high glucose concentrations controls the sustainability of the curved bilayer surface. Calculations revealed that certain orientations of (CO) over right arrow of interfacial glucose with the (PN) over right arrow of lipid headgroups are preferred, which helps the glucose to form direct hydrogen bonds (HBs) with the lipid headgroups. Such lipid-glucose (LG) HBs relax slowly at low glucose concentrations and exhibit a higher lifetime, whereas fast structural relaxation of LG HBs with a shorter lifetime was noticed at a higher glucose level. In contrast, lipid-water (LW) HBs exhibited a higher lifetime at a higher glucose level, which gradually decreased with the glucose level lowering. The study interprets that the glucose concentration-driven LW and LG interactions are mutually inclusive. Our detailed analysis will exemplify small saccharide concentration-driven membrane stabilizing efficiency, which is, in general, helpful for drug delivery study.

Development of new solvent/additive electrolyte is emerging field of research towards the improvement of ion transport and solid-electrolyte-interface formation in Li-ion battery (LIB). We perform extensive atomistic molecular dynamics simulations with LiPF6 in ethylene carbonate (EC) in presence of a new class of boron (B) based heterocyclic anion receptor additives; C2HBNO(NO2)(2), and C2HBNS(NO2)(2) and their trimers B[C2HBNO (NO2)(2)](3), and B[C2HBNS(NO2)(2)](3) to investigate the efficacy of this class of additives in regulating the solvation and transport properties of Li+ ions as compared to the reference LiPF6/EC solution that contained TPFPB, a commonly used B-based additive. Our designed additives in several aspects show their efficacy. Among all, C2HBNS(NO2)(2) is found to be the most efficient PF6- trapper that reduces ion pair formation. It promotes diffusion of Li+ and EC, improves the transference number, and reduces viscosity of solution, as compared to TPFPB. Further, it improves the ionic conductivity and drift velocity under a wide range of temperatures and external electric fields, respectively. Some of the computed properties are in agreement with the available experimental results. Our study would facilitate the design and synthesis of this class of additives to open up new possibilities of accelerating the LIB power sources for portable appliances.

The non-enzymatic glycation of plasma proteins by reducing sugars have important consequences on the conformational and functional properties of protein. The formation of advanced glycation end products (AGEs) is responsible for cell death and other pathological conditions. We have synthesized the glycated human serum albumin (gHSA) and characterized the same by using differential spectroscopic measurements. The aim of the present study is to determine the effect of glycation on the binding of human serum albumin (HSA) with bioactive flavonoid chrysin, which possesses anti-cancer, anti-inflammatory and anti-oxidant activities. The interaction of chrysin with HSA and gHSA was studied using multi-spectroscopic, molecular docking and molecular dynamics (MD) simulation techniques. Chrysin quenched the intrinsic fluorescence of both HSA and gHSA by static quenching mechanism. The value of the binding constant (K-b) for the interaction of HSA-chrysin complex (4.779 +/- 0.623 x 10(5) M-1 at 300 K) was found to be higher than that of gHSA-chrysin complex (2.206 +/- 0.234 x 10(5) M-1 at 300 K). Hence, non-enzymatic glycation of HSA significantly reduced its binding affinity towards chrysin. The % alpha-helicity of HSA was found to get enhanced upon binding with chrysin, and minimal changes were observed for the gHSA-chrysin complex. Site marker probe studies indicated that chrysin binds to subdomain IIA and IIIA of both HSA and gHSA. The results from molecular docking and MD simulation studies correlated well with the experimental findings. Electrostatic interactions followed by hydrogen bonding and hydrophobic interactions played major roles in the binding process. These observations may have some useful insights into the field of pharmaceutics.

Human serum albumin (HSA), an abundant protein in human plasma, which is associated with the transportation of numerous drugs, fatty acids to their targets and regulates the blood pH levels, is exposed to non-enzymatic glycation by reducing sugars. The existence of elevated levels of glucose during diabetes mellitus mediates the glycation of HSA which leads to structural and functional modification of the protein. The aim of our present study is to determine the effect of non-enzymatic glycation on the binding of a bioactive flavonoid luteolin to HSA using multi-spectroscopic and computational studies. The intrinsic fluorescence exhibited by the proteins (HSA and gHSA) were quenched by luteolin through static quenching mechanism. The binding constant for the interaction of HSA with luteolin was found higher as compared to that of gHSA-Luteolin at the experimental temperatures (290, 300 and 310 K). The Delta G values for the complexes formed between HSA/gHSA and luteolin were observed to be negative, indicating the spontaneity of the binding processes. Both enthalpy and entropy factors contribute to the binding of luteolin to HSA, whereas, enthalpy factors played a major role in the binding of luteolin to gHSA. A reduction in the alpha-helical content of HSA-Luteolin complex was observed, but no significant change was found for gHSA-Luteolin complex. Site probe displacement and related binding studies indicated that luteolin binds to both Subdomain IIA and IIIA of HSA and gHSA but with different affinities. Further molecular docking and MD simulation studies confirmed that luteolin preferably binds to the Subdomain IIA of HSA and IIIA of gHSA. These information, in turn, would give a better understanding of the functional changes occurred due to structural modification of HSA induced by glycation and may have some useful impact on the field of pharmaceutical sciences. (C) 2020 Elsevier B.V. All rights reserved.

In the proposed work, the complexation of bioactive flavonoid luteolin with hen egg white lysozyme (HEWL) along with its inhibitory influence on HEWL modification has been explored with the help of multi-spectroscopic and computational methods. The binding affinity has been observed to be moderate in nature (in the order of 104 M-1) and the static quenching mechanism was found to be involved in the fluorescence quenching process. The binding constant (Kb) shows a progressive increase with the increase in temperature from (4.075 ± 0.046 × 104 M-1) at 293 K to (6.962 ± 0.024 × 104 M-1) at 313 K under experimental conditions. Spectroscopic measurements along with molecular docking calculations suggest that Trp62 is involved in the binding site of luteolin within the geometry of HEWL. The positive changes in enthalpy (ΔH = +19.99 ± 0.65 kJ mol-1) as well as entropy (ΔS = +156.28 ± 2.00 J K-1 mol-1) are indicative of the presence of hydrophobic forces that stabilize the HEWL-luteolin complex. The micro-environment around the Trp residues showed an increase in hydrophobicity as indicated by synchronous fluorescence (SFS), three dimensional fluorescence (3D) and red edge excitation (REES) studies. The % α-helix of HEWL showed a marked reduction upon binding with luteolin as indicated by circular dichroism (CD) and Fourier-transform infrared spectroscopy (FTIR) studies. Moreover, luteolin is situated at a distance of 4.275 ± 0.004 nm from the binding site as indicated by FRET theory, and the rate of energy transfer kET (0.063 ± 0.004 ns-1) has been observed to be faster than the donor decay rate (1/τD = 0.606 ns-1), which is indicative of the non-radiative energy transfer during complexation. Leaving aside the binding study, luteolin showed promising inhibitory effects towards the d-ribose mediated glycation of HEWL as well as towards HEWL fibrillation as studied by fluorescence emission and imaging studies. Excellent correlation with the experimental observations as well as precise location and dynamics of luteolin within the binding site has been obtained from molecular docking and molecular dynamics simulation studies.