The construction of multilength scaled hierarchical nanostructures from diverse natural components is critical in the progress toward all-natural nanocomposites with structural robustness and versatile added functionalities. Here, we report a spontaneous formation of peculiar "shish kebab" nanostructures with the periodic arrangement of silk fibroin domains along straight segments of cellulose nanofibers. We suggest that the formation of these shish kebab nanostructures is facilitated by the preferential organization of heterogeneous (β-sheets and amorphous silk) domains along the cellulose nanofiber driven by modulated axial distribution of crystalline planes, hydrogen bonding, and hydrophobic interactions as suggested by all-atom molecular dynamic simulations. Such shish kebab nanostructures enable the ultrathin membrane to possess open, transparent, mechanically robust interlocked networks with high mechanical performance with up to 30 GPa in stiffness and 260 MPa in strength. These nanoporous robust membranes allow for the extremely high water flux, up to 3.5 × 10 L h m bar combined with high rejection rate for various organic molecules, capability of capturing heavy metal ions and their further reduction into metal nanoparticles for added SERS detection capability and catalytic functionalities.

Silk fibroin adsorption at the heterogeneous hydrophobic–hydrophilic surface of graphene oxide (GO) with different degrees of oxidation is addressed experimentally and theoretically. Samples are prepared using various spin‐assisted deposition conditions relevant to assembly of laminated nanocomposites from graphene‐based components, and compared with silicon dioxide (SiO2) as a benchmark substrate. Secondary structure of silk backbones changes as a function of silk fibroin concentration, substrate chemical composition, and deposition dynamics are assessed and compared with molecular dynamic simulations. It is observed that protofibrils form at low concentrations while variance in the deposition speed has little effect on silk secondary structure and morphology. However, balance of nonbonded interactions between electrostatic and van der Waals contributions can lead to silk secondary structure retention on the GO surface. Molecular dynamics simulations of silk fibroin at different surfaces show that strong van der Waals interactions play a pivotal role in losing and disrupting secondary structure on graphene and SiO2 surfaces. Fine tuning silk fibroin structure on heterogeneous graphene‐based surfaces paves the way toward development of biomolecular reinforcement for biopolymer–graphene laminated nanocomposites.

Constructing advanced functional nanomaterials with pre-designed organized morphologies from low-dimension synthetic and biological components is challenging. Herein, we report an efficient and universal amphiphilicity-driven assembly strategy to construct "hairy" flexible hybrid nanosheets with a 1D cellulose nanofibers (CNFs) net conformally wrapped around 2D graphene oxide (GO) monolayers. This interface-driven bio-synthetic assembly is facilitated by tailoring the surface chemistry of flexible GO sheets, resulting in individual sheets tightly surrounded by dense conformal nanocellulose network. The mechanical stability of the products far exceeds the compressive instability limits of both individual components. Additionally, the CNF network significantly enhances the wetting ability of initial hydrophobic reduced GO nanosheets, allowing fast water transport combined with high filtration efficiency.

Candida antarctica lipase B (CALB) is an efficient biocatalyst for hydrolysis, esterification, and polymerization reactions. In order to understand how to control enzyme activity and stability we performed a combined experimental and molecular dynamics simulation study of CALB in organic solvents and ionic liquids (ILs). Our results demonstrate that the conformational changes of the active site cavity are directly related to enzyme activity and decrease in the following order: [Bmim][TfO] > tert-butanol > [Bmim][Cl]. The entrance to the cavity is modulated by two isoleucines, ILE-189 and ILE-285, one of which is located on the α-10 helix. The α-10 helix can substantially change its conformation due to specific interactions with solvent molecules. This change is acutely evident in [Bmim][Cl] where interactions of LYS-290 with chlorine anions caused a conformational switch between α-helix and turn. Disruption of the α-10 helix structure results in a narrow cavity entrance and, thus, reduced the activity of CALB in [Bmim][Cl]. Finally, our results show that the electrostatic energy between solvents in this study and CALB is correlated with the structural changes leading to differences in enzyme activity.

In order to understand how cations affect the structural changes and enzyme activity of Lipase B from Candida antarctica, we performed all-atom molecular dynamics simulations of CALB in four types of ionic liquids (ILs) with varying sizes of imidazolium cations and correlated these results with the experimentally determined CALB activity. The imidazolium cations under study differ in the alkyl tail length in the following order: [Emim](+) < [Bmim](+) < [Hmim](+) < [Omim](+). We observed that the best enzyme activity and structural stability of CALB are obtained in [Bmim][TfO] and [Hmim][TfO]. In contrast, in [Emim][TfO], bonding of [TfO](-) to LYS-290 disrupts the interactions between LYS-290 and ILE-285, which leads to a closed catalytic gate conformation with low accessibility of substrates to the catalytic triad. In [Omim][TfO], strong hydrophobic interactions between [Omim](+) and LEU-278 result in a significant loss of the secondary structure of the α-10 helix and cause the exposure of the catalytic triad to ILs, which affects the stability of the catalytic triad and consequently deteriorates the enzyme activity. Overall, our study indicates that a high ion coordination number ([Emim][TfO]) or the presence of a long hydrophobic tail ([Omim][TfO]) can facilitate ion-protein interactions that cause structural distortions and a decrease in CALB enzyme activity in ILs.

A series of N-(2-amino-6-trifluoromethyl-pyridin-3-ylmethyl) 2-(3-fluoro-4-methylsulfonylaminophenyl) propanamides were designed combining previously identified pharmacophoric elements and evaluated as hTRPV1 antagonists. The SAR analysis indicated that specific hydrophobic interactions of the 2-amino substituents in the C-region of the ligand were critical for high hTRPV1binding potency. In particular, compound 49S was an excellent TRPV1 antagonist (Ki(CAP) = 0.2 nM; IC50(pH) = 6.3 nM) and was thus ca. 100- and 20-fold more potent, respectively, than the parent compounds 2 and 3 for capsaicin antagonism. Furthermore, it demonstrated strong analgesic activity in the rat neuropathic model superior to 2 with almost no side effects. Compound 49S antagonized capsaicin induced hypothermia in mice, but showed TRPV1-related hyperthermia. The basis for the high potency of 49S compared to 2 is suggested by docking analysis with our hTRPV1 homology model in which the 4-methylpiperidinyl group in the C-region of 49S made additional hydrophobic interactions with the hydrophobic region.

The clinical benefit of current anticancer regimens for lung cancer therapy is still limited due to moderate efficacy, drug resistance, and recurrence. Therefore, the development of effective anticancer drugs for first-line therapy and for optimal second-line treatment is necessary. Because the 90-kDa molecular chaperone heat shock protein (Hsp90) contributes to the maturation of numerous mutated or overexpressed oncogenic proteins, targeting Hsp90 may offer an effective anticancer therapy. Here, we investigated antitumor activities and toxicity of a novel deguelinderived C-terminal Hsp90 inhibitor, designated L80. L80 displayed significant inhibitory effects on the viability, colony formation, angiogenesis-stimulating activity, migration, and invasion of a panel of non-small cell lung cancer cell lines and their sublines with acquired resistance to paclitaxel with minimal toxicity to normal lung epithelial cells, hippocampal cells, vascular endothelial cells, and ocular cells. Biochemical analyses and molecular docking simulation revealed that L80 disrupted Hsp90 function by binding to the C-terminal ATP-binding pocket of Hsp90, leading to the disruption of the interaction between hypoxia-inducible factor (HIF)-1a and Hsp90, downregulation of HIF-1a and its target genes, including vascular endothelial growth factor (VEGF) and insulin-like growth factor 2 (IGF2), and decreased the expression of various Hsp90 client proteins. Consistent with these in vitro findings, L80 exhibited significant antitumor and antiangiogenic activities in H1299 xenograft tumors. These results suggest that L80 represents a novel C-terminal Hsp90 inhibitor with effective anticancer activities with minimal toxicities.

In order to understand how oxidation rate of graphene surfaces affects single‐stranded poly‐thymine, poly(T)20, structure during physisorption, all‐atom molecular dynamics simulations are performed. In aqueous solutions, poly(T)20 is a complex structure with stacked and coiled regions. However, on the graphene surfaces, there are three different regimes for the adsorption process, which heavily depends on the surface oxidation: (1) on pristine graphene or graphene oxide (GO) with low oxygen coverage (GO 5%) the stacked poly(T)20 structure becomes unfolded due to formation of strong π–π interactions with the surface, (2) on graphene oxide with moderate oxygen coverage (GO 10%–25%) the structure of poly(T)20 is well preserved because of the balance between van der Waals and electrostatic interactions, and (3) on graphene oxide with high oxygen content (GO 30%–60%) stacked poly(T)20 structure is locally disrupted due to formation of strong hydrogen bonds with the surface. Moreover, surface roughness due to the presence of oxygen groups plays a pivotal role in structural retention of poly(T)20 by preventing its nucleobases from forming π–π stacking interactions with the surface.