Computational techniques have the potential to accelerate the design and optimization of nanomaterials for applications such as drug delivery and contaminant removal; however, the success of such techniques requires reliable models of nanomaterial surfaces as well as accurate descriptions of their interactions with relevant solutes. In the present work, we evaluate the ability of selected models of naked and hydroxylated carbon nanotubes to predict adsorption equilibrium constants for about 30 small aromatic compounds with a variety of functional groups. The equilibrium constants determined using molecular dynamics coupled with free-energy calculation techniques are directly compared to those derived from experimental measurements. The calculations are highly predictive of the relative adsorption affinities of the compounds, with excellent correlation (r ≥ 0.9) between calculated and measured values of the logarithm of the adsorption equilibrium constant. Moreover, the agreement in absolute terms is also reasonable, with average errors of less than one decade. We also explore possible effects of surface loading, although we demonstrate that they are negligible for the experimental conditions considered. Given the degree of reliability demonstrated, we move on to employing the in silico techniques in the design of nanomaterials, using the optimization of adsorption affinity for the herbacide atrazine as an example. Our simulations suggest that, compared to other modifications of graphenic carbon, polyvinylpyrrolidone conjugation gives the highest affinity for atrazine-substantially greater than that of graphenic carbon alone-and may be useful as a nanomaterial for delivery or sequestration of atrazine.

Background:The mode of action of PI(4,5)P 2 in TRPV1 is controversial. Results: Positively charged amino acids in the S4-S5 linker and in the TRP box form the PI(4,5)P 2 binding site. Conclusion: PI(4,5)P 2 is a TRPV1 agonist and induces a conformational change of the internal gate. Significance: The molecular nature of the PI(4,5)P 2 binding site in TRPV1 is defined.

The photophysics and photochemistry of rose bengal (RB) and methylene blue (MB) bound to human serum albumin (HSA) have been investigated under a variety of experimental conditions. Distribution of the dyes between the external solvent and the protein has been estimated by physical separation and fluorescence measurements. The main localization of protein-bound dye molecules was estimated by the intrinsic fluorescence quenching, displacement of fluorescent probes bound to specific protein sites, and by docking modelling. All the data indicate that, at low occupation numbers, RB binds strongly to the HSA site I, while MB localizes predominantly in the protein binding site II. This different localization explains the observed differences in the dyes' photochemical behaviour. In particular, the environment provided by site I is less polar and considerably less accessible to oxygen. The localization of RB in site I also leads to an efficient quenching of the intrinsic protein fluorescence (ascribed to the nearby Trp residue) and the generation of intra-protein singlet oxygen, whose behaviour is different to that observed in the external solvent or when it is generated by bound MB.

We investigated two critical aspects of rose Bengal (RB) photosensitized protein cross-linking that may underlie recently developed medical applications. Our studies focused on the binding of RB to collagen by physical interaction and the effect of this binding and certain amino acids on RB photochemistry. Molecular dynamics simulations and free-energy calculation techniques, complemented with isothermal titration calorimetry, provided insight into the binding between RB and a collagen-like peptide (CLP) at the atomic level. Electrostatic interactions dominated, which is consistent with the finding that RB bound equally well to triple helical and single chain collagen. The binding free energy ranged from −5.7 to −3 kcal/mol and was strongest near the positively charged amino groups at the N-terminus and on lysine side chains. At high RB concentration, a maximum of 16 ± 3 bound dye molecules per peptide was found, which is consistent with spectroscopic evidence for aggregated RB bound to collagen or the CLP. Within a tissue-mimetic collagen matrix, RB photobleached rapidly, probably due to electron transfer to certain protein amino acids, as was demonstrated in solutions of free RB and arginine. In the presence of arginine and low oxygen concentrations, a product absorbing at 510 nm formed, presumably due to dehalogenation after electron transfer to RB. In the collagen matrix without arginine, the dye generated singlet oxygen as well as the 510 nm product. These results provide the first evidence of the effects of a tissue-like environment on the photochemical mechanisms of rose Bengal.

Thermally denatured human serum albumin interacts with *3.0 nm spherical AgNP enhancing the fluorescence of Trp-214 at large protein/ nanoparticle ratios. However, using native HSA, no changes in the emission were observed. The observation is likely due to differences between native and denatured protein packing resulting from protein corona formation. We have also found that NH 2 blocking of the protein strongly affects the ability of the protein to protect AgNP from different salts/ions such as NaCl, PBS, Hank's buffer, Tris-HCl, MES, and DMEM. Additionally, AgNP can be readily prepared in aqueous solutions by a photochemical approach employing HSA as an in situ protecting agent. The role of the protein in this case is beyond that of protecting agent; thus, Ag ? ions and I-2959 complexation within the protein structure also affects the efficiency of AgNP formation. Blocking NH 2 in HSA modified the AgNP growth profile, surface plasmon band shape, and long-term stability suggesting that amine groups are directly involved in the formation and post-stabilization of AgNP. In particular, AgNP size and shape are extensively influenced by NH 2 blocking, leading primarily to cubes and plates with sizes around 5-15 nm; in contrast, spherical monodisperse 4.0 nm AgNP are observed for native HSA. The nanoparticles prepared by this protocol are non-toxic in primary cells and have remarkable antibacterial properties. Finally, surface plasmon excitation of native HSA@AgNP promoted loss of protein conformation in just 5 min, suggesting that plasmon heating causes protein denaturation using continuous light sources such as commercial LED.

Adsorption of organic molecules from aqueous solution to the surface of carbon nanotubes or graphene is an important process in many applications of these materials. Here we use molecular dynamics simulation, supplemented by analytical chemistry, to explore in detail the adsorption thermodynamics of a diverse set of aromatic compounds on graphenic materials, elucidating the effects of the solvent, surface coverage, surface curvature, defects, and functionalization by hydroxy groups. We decompose the adsorption free energies into entropic and enthalpic components and find that different classes of compoundssuch as phenols, benzoates, and alkylbenzenescan easily be distinguished by the relative contributions of entropy and enthalpy to their adsorption free energies. Overall, entropy dominates for the more hydrophobic compounds, while enthalpy plays the greatest role for more hydrophilic compounds. Experiments and independent simulations using two different force field frameworks (CHARMM and Amber) support the robustness of these conclusions. We determine that concave curvature is generally associated with greater adsorption affinity, more favorable enthalpy, and greater contact area, while convex curvature reduces both adsorption enthalpy and contact area. Defects on the graphene surfaces can create concave curvature, resulting in localized binding sites. As the graphene surface becomes covered with aromatic solutes, the affinity for adsorbing an additional solute increases until a complete monolayer is formed, driven by more favorable enthalpy and partially canceled by less favorable entropy. Similarly, hydroxylation of the surface leads to preferential adsorption of the aromatic solutes to remaining regions of bare graphene, resulting in less favorable adsorption entropy, but compensated by an increase in favorable enthalpic interactions.

That channels and transporters can influence the membrane morphology is increasingly recognized. Less appreciated is that the extent and free-energy cost of these deformations likely varies among different functional states of a protein, and thus, that they might contribute significantly to defining its mechanism. We consider the trimeric Na+-aspartate symporter GltPh, a homolog of an important class of neurotransmitter transporters, whose mechanism entails one of the most drastic structural changes known. Molecular simulations indicate that when the protomers become inward-facing, they cause deep, long-ranged, and yet mutually-independent membrane deformations. Using a novel simulation methodology, we estimate that the free-energy cost of this membrane perturbation is in the order of 6–7 kcal/mol per protomer. Compensating free-energy contributions within the protein or its environment must thus stabilize this inward-facing conformation for the transporter to function. We discuss these striking results in the context of existing experimental observations for this and other transporters.

We studied the interaction of four new pentapeptides with spherical silver nanoparticles. Our findings indicate that the combination of the thiol in Cys and amines in Lys/Arg residues is critical to providing stable protection for the silver surface. Molecular simulation reveals the atomic scale interactions that underlie the observed stabilizing effect of these peptides, while yielding qualitative agreement with experiment for ranking the affinity of the four pentapeptides for the silver surface.