Quantum sensing of microRNAs with nitrogen-vacancy centers in diamond.

Label-free detection of nucleic acids such as microRNAs holds great potential for early diagnostics of various types of cancers. Measuring intrinsic biomolecular charge using methods based on field effect has been a promising way to accomplish label-free detection. However, the charges of biomolecules are screened by counter ions in solutions over a short distance (Debye length), thereby limiting the sensitivity of these methods.

Aptamer-based gold nanoparticle aggregates for ultrasensitive amplification-free detection of PSMA.

Early diagnosis is one of the most important factors in determining the prognosis in cancer. Sensitive detection and quantification of tumour-specific biomarkers have the potential to improve significantly our diagnostic capability. Here, we introduce a triggerable aptamer-based nanostructure based on an oligonucleotide/gold nanoparticle architecture that selectively disassembles in the presence of the biomarker of interest; its optimization is based also on in-silico determination of the aptamer nucleotides interactions with the protein of interest.

Quantum computing algorithms: getting closer to critical problems in computational biology.

The recent biotechnological progress has allowed life scientists and physicians to access an unprecedented, massive amount of data at all levels (molecular, supramolecular, cellular and so on) of biological complexity. So far, mostly classical computational efforts have been dedicated to the simulation, prediction or de novo design of biomolecules, in order to improve the understanding of their function or to develop novel therapeutics. At a higher level of complexity, the progress of omics disciplines (genomics, transcriptomics, proteomics and metabolomics) has prompted researchers to develop informatics means to describe and annotate new biomolecules identified with a resolution down to the single cell, but also with a high-throughput speed.

Energy, Structures, and Response Properties with a Fully Coupled QM/AMOEBA/ddCOSMO Implementation.

We present the implementation of a fully coupled polarizable QM/MM/continuum model based on the AMOEBA polarizable force field and the domain decomposition implementation of the conductor-like screening model. Energies, response properties, and analytical gradients with respect to both QM and MM nuclear positions are available, and a generic, atomistic cavity can be employed. The model is linear scaling in memory requirements and computational cost with respect to the number of classical atoms and is therefore suited to model large, complex systems.

New 1,3-Disubstituted Benzo[]Isoquinoline Cyclen-Based Ligand Platform: Synthesis, Eu Multiphoton Sensitization and Imaging Applications.

The development of lanthanide-based luminescent probes with a long emission lifetime has the potential to revolutionize imaging-based diagnostic techniques. By a rational design strategy taking advantage of computational predictions, a novel, water-soluble Eu complex from a cyclen-based ligand bearing 1,3-disubstituted benzo[h]isoquinoline arms was realized. The ligand has been obtained overcoming the lack of reactivity of position 3 of the isoquinoline moiety.

Molecular insight on the altered membrane trafficking of TrkA kinase dead mutants.

We address the contribution of kinase domain structure and catalytic activity to membrane trafficking of TrkA receptor tyrosine kinase. We conduct a systematic comparison between TrkA-wt, an ATP-binding defective mutant (TrkA-K544N) and other mutants displaying separate functional impairments of phosphorylation, ubiquitination, or recruitment of intracellular partners. We find that only K544N mutation endows TrkA with restricted membrane mobility and a substantial increase of cell surface pool already in the absence of ligand stimulation.

The key to the yellow-to-cyan tuning in the green fluorescent protein family is polarisation.

Computational approaches have to date failed to fully capture the large (about 0.4 eV) excitation energy tuning displayed by the nearly identical anionic chromophore in different green fluorescent protein (GFP) variants. Here, we present a thorough comparative study of a set of proteins in this sub-family, including the most red- (phiYFP) and blue-shifted (mTFP0.

Unique Photophysical Behavior of Coumarin-Based Viscosity Probes during Molecular Self-Assembly.

Intermolecular interactions impact self-assembly phenomena having a variety of bio/chemical, physical, and mechanical consequences. Nevertheless, the underlying mechanisms leading to a controlled stereo- and chemo-specific aggregation at the molecular level often remain elusive because of the intrinsically dynamic nature of these processes. Herein, we describe two 3-styryl coumarin molecular rotors capable of probing subtle intermolecular interactions controlling the self-assembly of a small-molecule organogelator.

Lipid-Conjugated Rigidochromic Probe Discloses Membrane Alteration in Model Cells of Krabbe Disease.

The plasma membrane of cells has a complex architecture based on the bidimensional liquid-crystalline bilayer arrangement of phospho- and sphingolipids, which in turn embeds several proteins and is connected to the cytoskeleton. Several studies highlight the spatial membrane organization into more ordered (L or lipid raft) and more disordered (L) domains. We here report on a fluorescent analog of the green fluorescent protein chromophore that, when conjugated to a phospholipid, enables the quantification of the L and L domains in living cells on account of its large fluorescence lifetime variation in the two phases.

Role of Gln222 in Photoswitching of Aequorea Fluorescent Proteins: A Twisting and H-Bonding Affair?

Reversibly photoswitchable fluorescent proteins (RSFPs) admirably combine the genetic encoding of fluorescence with the ability to repeatedly toggle between a bright and dark state, adding a new temporal dimension to the fluorescence signal. Accordingly, in recent years RSFPs have paved the way to novel applications in cell imaging that rely on their reversible photoswitching, including many super-resolution techniques such as F-PALM, RESOLFT, and SOFI that provide nanoscale pictures of the living matter. Yet many RSFPs have been engineered by a rational approach only to a limited extent, in the absence of clear structure-property relationships that in most cases make anecdotic the emergence of the photoswitching.

Simultaneous Detection of Local Polarizability and Viscosity by a Single Fluorescent Probe in Cells.

Many intracellular reactions are dependent on the dielectric ("polarity") and viscosity properties of their milieu. Fluorescence imaging offers a convenient strategy to report on such environmental properties. Yet, concomitant and independent monitoring of polarity and viscosity in cells at submicron scale is currently hampered by the lack of fluorescence probes characterized by unmixed responses to both parameters.

Self-aggregation propensity of the Tat peptide revealed by UV-Vis, NMR and MD analyses.

By a combination of UV-Vis analyses, NMR-based diffusion measurements and MD simulations we have demonstrated for the first time that the HIV-1 Tat arginine-rich peptide (Tat) is able to self-aggregate in both its fluorescently labeled and unlabeled variants. We propose Tat dimerization as the dominant aggregation process and show that the associated equilibrium constant increases ten-fold by labeling with the standard TAMRA dye. Also, we extend similar conclusions to other cationic cell penetrating peptides (CPPs), such as Antennapedia (Ant) and nona-arginine (R9).

Correction: Facile synthesis of stable, water soluble, dendron-coated gold nanoparticles.

Correction for 'Facile synthesis of stable, water soluble, dendron-coated gold nanoparticles' by Alan E. Enciso, et al., Nanoscale, 2017, 9, 3128-3132.

Main photophysical properties of oxyblepharismin.

Oxyblepharismin is the photo-oxidized form of blepharismin, the chromophore responsible for the photophobic response of heterotrich ciliate Blepharisma japonicum, and represents a nice model for the study of photo-transduction. In this work, we focused on the photophysical characterization of OxyBP, in view of highlighting the main features related to excitation and emission. By a combined experimental and computational approach we identified the main features of absorption and fluorescence emission of the molecule in solvents of different properties, identifying the nature of transitions as well as the possible heterogeneity at ground/excited state.

Facile synthesis of stable, water soluble, dendron-coated gold nanoparticles.

Upon reduction with sodium borohydride, diazonium tetrachloroaurate salts of triazine dendrons yield dendron-coated gold nanoparticles connected by a gold-carbon bond. These robust nanoparticles are stable in water and toluene solutions for longer than one year and present surface groups that can be reacted to change surface chemistry and manipulate solubility. Molecular modeling was used to provide insight on the hydration of the nanoparticles and their observed solubilties.

Temperature and pressure effects on GFP mutants: explaining spectral changes by molecular dynamics simulations and TD-DFT calculations.

By combining spectroscopic measurements under high pressure with molecular dynamics simulations and quantum mechanics calculations we investigate how sub-angstrom structural perturbations are able to tune protein function. We monitored the variations in fluorescence output of two green fluorescent protein mutants (termed Mut2 and Mut2Y, the latter containing the key T203Y mutation) subjected to pressures up to 600 MPa, at various temperatures in the 280-320 K range. By performing 150 ns molecular dynamics simulations of the protein structures at various pressures, we evidenced subtle changes in conformation and dynamics around the light-absorbing chromophore.

Non-linear optical response by functionalized gold nanospheres: identifying design principles to maximize the molecular photo-release.

In a recent study by Voliani et al. [Small, 2011, 7, 3271], the electromagnetic field enhancement in the vicinity of the gold nanoparticle surface has been exploited to achieve photocontrolled release of a molecular cargo conjugated to the nanoparticles via 1,2,3-triazole, a photocleavable moiety. The aim of the present study is to investigate the mechanism of the photorelease by characterizing the nanoparticle aggregation status within the cells and simulating the electric field enhancement in a range of experimentally realistic geometries, such as single Au nanoparticles, dimers, trimers and random aggregates.

In silico design of antimicrobial peptides.

The rapid spread of drug-resistant pathogenic microbial strains has created an urgent need for the development of new anti-infective molecules, having different mechanism of action in comparison to existing drugs. Natural antimicrobial peptides (AMPs) represent a novel class of molecules with a broad spectrum of activity and a low rate in inducing bacterial resistance. In particular, linear alpha-helical cationic antimicrobial peptides are among the most widespread membrane-disruptive AMPs in nature, representing a particularly successful structural arrangement of the innate defense against microbes.

Treatment of microbial biofilms in the post-antibiotic era: prophylactic and therapeutic use of antimicrobial peptides and their design by bioinformatics tools.

The treatment for biofilm infections is particularly challenging because bacteria in these conditions become refractory to antibiotic drugs. The reduced effectiveness of current therapies spurs research for the identification of novel molecules endowed with antimicrobial activities and new mechanisms of antibiofilm action. Antimicrobial peptides (AMPs) have been receiving increasing attention as potential therapeutic agents, because they represent a novel class of antibiotics with a wide spectrum of activity and a low rate in inducing bacterial resistance.

Two interconvertible folds modulate the activity of a DNA aptamer against transferrin receptor.

Thanks to their ability to recognize biomolecular targets with high affinity and specificity, nucleic acid aptamers are increasingly investigated as diagnostic and therapeutic tools, particularly when their targets are cell-surface receptors. Here, we investigate the relationship between the folding of an anti-mouse transferrin receptor DNA aptamer and its interaction with the transferrin receptor both in vitro and in living cells. We identified and purified two aptamer conformers by means of chromatographic techniques.

Antimicrobial peptides design by evolutionary multiobjective optimization.

Antimicrobial peptides (AMPs) are an abundant and wide class of molecules produced by many tissues and cell types in a variety of mammals, plant and animal species. Linear alpha-helical antimicrobial peptides are among the most widespread membrane-disruptive AMPs in nature, representing a particularly successful structural arrangement in innate defense. Recently, AMPs have received increasing attention as potential therapeutic agents, owing to their broad activity spectrum and their reduced tendency to induce resistance.

Spectral "Fine" Tuning in Fluorescent Proteins: The Case of the GFP-Like Chromophore in the Anionic Protonation State.

Fluorescent proteins (FPs), featuring the same chromophore but different chromophore-protein interactions, display remarkable spectral variations even when the same chromophore protonation state, i.e. the anionic state, is involved.

A novel chimeric cell-penetrating peptide with membrane-disruptive properties for efficient endosomal escape.

Efficient endocytosis into a wide range of target cells and low toxicity make the arginine-rich Tat peptide (Tat(11): YGRKKRRQRRR, residues 47-57 of HIV-1 Tat protein) an excellent transporter for delivery purposes. Unfortunately, molecules taken up by endocytosis undergo endosomal entrapment and possible metabolic degradation. Escape from the endosome is therefore actively researched.

Multiphoton molecular photorelease in click-chemistry-functionalized gold nanoparticles.

Yellow-green controlled photorelease: probes click-linked to peptide-coated gold nanospheres by a triazole ring can be released in living cells under a focused 561 nm laser at low power. Photocleaving follows a three-photon event stimulated by the excitation of the localized surface plasmon resonance.

Cis-trans photoisomerization properties of GFP chromophore analogs.

The photoswitching behaviour of the green fluorescent protein (GFP) chromophore and its analogs opens up exciting horizons for the engineering and development of molecular devices for high sensitivity in vivo studies. In this work we present the synthesis and photophysical study of four GFP chromophore analogs belonging to butenolide and pyrrolinone classes. These chromophores possess an intriguing photoinduced cis-trans isomerization mechanism.