Urea at sufficiently high concentration unfolds the secondary structure of proteins leading to denaturation. In contrast, choline chloride (ChCl) and urea, in 1 : 2 molar ratio, form a deep eutectic mixture, a liquid at room temperature, protecting proteins from denaturation. In order to get a microscopic picture of this phenomenon, we perform extensive all‐atom molecular dynamics simulations on a model protein, HP‐36. Based on our calculation of Kirkwood‐Buff integrals, we analyze the relative accumulation of urea and ChCl around the protein. Additional insights are drawn from the translational and rotational dynamics of solvent molecules and hydrogen bond auto‐correlation functions. In the presence of urea, water shows slow subdiffusive dynamics around the protein owing to a strong interaction of water with the backbone atoms. Urea also shows subdiffusive motion. The addition of ChCl further slows down the dynamics of urea, restricting its accumulation around the protein backbone. Adding to this, choline cations in the first solvation shell of the protein show the strongest subdiffusive behavior. In other words, ChCl acts as a nano‐crowder by excluding urea from the protein backbone and thereby slowing down the dynamics of water around the protein. This prevents the protein from denaturation and makes it structurally rigid, which is supported by the smaller radius of gyration and root mean square deviation values of HP‐36.

Water–urea hydrogen bonds partially restore the tetrahedral coordination of water molecules in aqueous reline solutions.

Surface roughness is one of the most important requirements of the finished products in machining process. The determination of optimal cutting parameters is very important to minimize the surface roughness of a product. This article describes the development process of a surface roughness model in high-speed ball-end milling using response surface methodology based on design of experiment. Composite desirability function and teaching-learning-based optimization algorithm have been used for determining optimal cutting process parameters. The experiments have been planned and conducted using rotatable central composite design under dry condition. Mathematical model for surface roughness has been developed in terms of cutting speed, feed per tooth, axial depth of cut and radial depth of cut as the cutting process parameters. Analysis of variance has been performed for analysing the effect of cutting parameters on surface roughness. A second-order full quadratic model is used for mathematical modelling. The analysis of the results shows that the developed model is adequate enough and good to be accepted. Analysis of variance for the individual terms revealed that surface roughness is mostly affected by the cutting speed with a percentage contribution of 47.18% followed by axial depth of cut by 10.83%. The optimum values of cutting process parameters obtained through teaching-learning-based optimization are feed per tooth ( fz) = 0.06 mm, axial depth of cut ( Ap) = 0.74 mm, cutting speed ( Vc) = 145.8 m/min, and radial depth of cut ( Ae) = 0.38 mm. The optimum value of surface roughness at the optimum parametric setting is 1.11 µm and has been validated by confirmation experiments.

The Bcl2 family of proteins is capable of switching the apoptotic machinery by directly controlling the release of apoptotic factors from the mitochondrial outer membrane. They have ‘pro’ and ‘anti’-apoptotic subgroups of proteins which antagonize each other’s function; however a detailed atomistic understanding of their mechanisms based on the dynamical events, particularly in the membrane, is lacking. Using molecular dynamics simulations totaling 1.6µs we outline the major differences between the conformational dynamics in water and in membrane. Using implicit models of solvent and membrane, the simulated results reveal a picture that is in agreement with the ‘hit-and run’ concept which states that BH3-only peptides displace the tail (which acts as a pseudo substrate of the protein itself) from its binding pocket; this helps the membrane association of the protein after which the BH3 peptide becomes free. From simulations, Bcl-xL appears to be auto-inhibited by its C-terminal tail that embeds into and covers the hydrophobic binding pocket. However the tail is unable to energetically compete with BH3-peptides in water. In contrast, in the membrane, neither the tail nor the BH3-peptides are stable in the binding pocket and appear to be easily dissociated off as the pocket expands in response to the hydrophobic environment. This renders the binding pocket large and open, thus receptive to interactions with other protein partners. Principal components of the motions are dramatically different in the aqueous and in the membrane environments and provide clues regarding the conformational transitions that Bcl-xL undergoes in the membrane, in agreement with the biochemical data.

Molecular dynamics simulations elucidate the structural collapse shown by two ssDNAs of the same base sequence in the presence of either Na+ or Mg2+, starting from in vivo ionic concentration to higher concentrations. Initially, an increase in ion concentration facilitates the structural distortion of individual ssDNA and helps to bring them close, and for this, Mg2+ is better than Na+. However, further addition of ions leads to structural reswelling of the DNA strands and inhibits their proximity. The structural changes are found to be guided by the strong interaction of the cations with the phosphinyl oxygen (pn_O). Additionally, a significant difference has been noticed in the interaction of the cations with phosphoester oxygen (pe_O) depending on the nature of the ion. The sequential and nonsequential base-pair stacking is one of the major factors in the structural collapse of individual ssDNA. Overall, the present investigation highlights some of the important aspects of aggregation of two ssDNA with the same base sequence at varying cationic concentration.

Choline chloride (ChCl) is a component of several deep eutectic solvents (DESs) having numerous applications. Recent studies have reported manifold promising use of aqueous choline chloride solution as an alternative to DES, where water plays the role of the hydrogen-bond donor. The characteristic physical properties of the DESs and aqueous DES originate from the "inter-" and intraspecies hydrogen-bond network formed by the constituents. However, a detailed molecular-level picture of choline chloride and water mixture is largely lacking in the literature. This motivates us to carry out extensive all-atom molecular dynamics simulations of the ChCl−water mixture of varying compositions. Our analyses clearly show an overall increase in the interspecies association with an increase in ChCl concentration. At higher concentrations, the trimethylammonium groups of choline are stabilized by a nonpolar interaction, whereas the hydroxyl groups preferentially interact with water. Chloride ions are found to be involved in two types of interactions: one where chloride ions intercalate two or more choline cations, and the other one where they are surrounded by five to six water molecules forming solvated chloride ions. However, the relative fractions of these two types of associations depend on the concentration of ChCl in the mixture. Another important structural aspect is the disruption of the hydrogen-bonded water network due to the presence of both choline cations and chloride ions. However, chloride ions participate to partially restore the tetrahedral arrangement of partners around water molecules.

Bcl-xl protein has a long unstructured loop attached to its structured region which joins two helices. The necessity to have this unstructured segment in Bcl-xl is not yet well understood. To what extent the unstructured segment can influence the dynamics of the structured region of protein, with potential to influence the function, has been investigated in this work. Molecular dynamics simulation and principal component analysis show how the loop affects the internal motions of the protein, particularly its ligand binding pocket. Generally an unstructured region in the structure would promote flexibility resulting entropic stability but in contrary, here it narrows down the conformational space of the structured region of protein that could be hypothesized to impact the functional precision. Effects of the loop propagate to the binding pocket through structural rearrangements of polar side chains. The immediate suspicion of possible impact of phosphorylation to modulate the function of the protein is proven to be a fact, as the phosphorylated S49 and S62 located on the large unstructured region are seen to perturb the electrostatic network of the structure; an observation that validates and clarifies the role of loop as a modulator through biophysical and biochemical mechanisms. Proteins 2017; 85:1567-1579. © 2017 Wiley Periodicals, Inc.

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