A Designed Conformational Shift To Control Protein Binding Specificity

In a conformational selection scenario, manipulating the populations of binding‐competent states should be expected to affect protein binding. We demonstrate how in silico designed point mutations within the core of ubiquitin, remote from the binding interface, change the binding specificity by shifting the conformational equilibrium of the ground‐state ensemble between open and closed substates that have a similar population in the wild‐type protein. Binding affinities determined by NMR titration experiments agree with the predictions, thereby showing that, indeed, a shift in the conformational equilibrium enables us to alter ubiquitin’s binding specificity and hence its function. Thus, we present a novel route towards designing specific binding by a conformational shift through exploiting the fact that conformational selection depends on the concentration of binding‐competent substates.     

Theory of resonance energy transfer involving nanocrystals: the role of high multipoles

A theory for the fluorescence resonance energy transfer (FRET) between a pair of semiconducting nanocrystal quantum dots is developed. Two types of donor-acceptor couplings for the FRET rate are described: dipole-dipole (d-d) and the dipole-quadrupole (d-q) couplings. The theory builds on a simple effective mass model that is used to relate the FRET rate to measureable quantities such as the nanocrystal size, fundamental gap, effective mass, exciton radius, and optical permittivity. We discuss the relative contribution to the FRET rate of the different multipole terms, the role of strong to weak confinement limits, and the effects of nanocrystal sizes.     

A simple FRET-based modular design for diagnostic probes

In recent years, there has been a massive effort to develop molecular probes with optical modes of action. Probes generally produce detectable signals based on changes in fluorescence properties. Here, we demonstrate the potential of self-immolative molecular adaptors as a platform for Turn-On probes based on the FRET technique. The probe is equipped with identical fluorophore pairs or a fluorophore/quencher FRET pair and a triggering substrate. Upon reaction of the analyte of interest with the triggering substrate, the self-immolative adaptor spontaneously releases the two dye molecules to break off the FRET effect. As a result, a new measurable fluorescent signal is generated. The fluorescence obtained can be used to quantify the analyte. The modular structure of the probe design will allow the preparation of various chemical probes based on the FRET activation technique.     

Nucleoside-5'-phosphorothioate analogues are biocompatible antioxidants dissolving efficiently amyloid beta-metal ion aggregates

Amyloid beta (Aβ) peptide is known to precipitate and form aggregates with zinc and copper ions in vitro and, in vivo in Alzheimer's disease (AD) patients. Metal-ion-chelation was suggested as therapy for the metal-ion-induced Aβ aggregation, metal-ion overload, and oxidative stress. In a quest for biocompatible metal-ion chelators potentially useful for AD therapy, we tested a series of nucleoside 5'-phosphorothioate derivatives as re-solubilization agents of Cu(+)/Cu(2+)/Zn(2+)-induced Aβ-aggregates, and inhibitors of Fenton reaction in Cu(+) or Fe(2+)/H(2)O(2) system. The most promising chelator in this series was found to be APCPP-γ-S. This nucleotide was found to be more efficient than EDTA in re-solubilization of Aβ(40)-Cu(2+) aggregates as observed by the lower diameter, d(H), (86 vs. 64 nm, respectively) obtained in dynamic light scattering measurements. Likewise, APCPP-γ-S dissolved Aβ(40)-Cu(+) and Aβ(42)-Cu(2+)/Zn(2+) aggregates, as monitored by (1)H-NMR and turbidity assays, respectively. Furthermore, addition of APCPP-γ-S to nine-day old Aβ(40)-Cu(2+)/Zn(2+) aggregates, resulted in size reduction as observed by transition electron microscopy (diameter reduction from 2.5 to 0.1 μm for Aβ(40)-Cu(2+) aggregates). APCPP-γ-S proved to be more efficient than ascorbic acid and GSH in reducing OH radical production in Fe(2+)/H(2)O(2) system (IC(50) values 85, 216 and, 92 μM, respectively). Therefore, we propose APCPP-γ-S as a potential AD therapy capable of both reducing OH radical production and re-solubilization of Aβ(40/42)-M(n+) aggregates.     

Efficient hydrogenation of biomass-derived cyclic di-esters to 1,2-diols

The unprecedented homogeneous hydrogenation of cyclic di-esters, in particular biomass-derived glycolide and lactide, to the corresponding 1,2-diols is catalyzed by Ru(II) PNN (1) and Ru(II) CNN (2) pincer complexes under mild hydrogen pressure and (in the case of 1) neutral conditions. No racemization was observed when a chiral di-ester was used.     

Constructing metrics on a 2-torus with a partially prescribed stable norm

A result of Bangert states that the stable norm associated to any Riemannian metric on the 2-torus T ² is strictly convex. We demonstrate that the space of stable norms associated to metrics on T ² forms a proper dense subset of the space of strictly convex norms on ${{\mathbb R}^2}$ . In particular, given a strictly convex norm || · ||_∞ on ${{\mathbb R}^2}$ we construct a sequence ${\langle {\| \cdot \|}_j \rangle_{j=1}^{\infty}}$ of stable norms that converge to || · ||_∞ in the topology of compact convergence and have the property that for each r > 0 there is an ${N \equiv N(r)}$ such that || · || _j agrees with || · ||_∞ on ${{\mathbb Z}^2 \cap \{(a,b) : a^2 + b^2 \leq r \}}$ for all j ≥ N. Using this result, we are able to derive results on multiplicities which arise in the minimum length spectrum of 2-tori and in the simple length spectrum of hyperbolic tori.     

Transferable pair potentials for CdS and ZnS crystals

A set of interatomic pair potentials is developed for CdS and ZnS crystals. We show that a simple energy function, which has been used to describe the properties of CdSe [E. Rabani, J. Chem. Phys. 116, 258 (2002)], can be parametrized to accurately describe the lattice and elastic constants, and phonon dispersion relations of bulk CdS and ZnS in the wurtzite and rocksalt crystal structures. The predicted coexistence pressure of the wurtzite and rocksalt structures as well as the equation of state are in good agreement with experimental observations. These new pair potentials enable the study of a wide range of processes in bulk and nanocrystalline II-VI semiconductor materials.     

Fracture surfaces as multiscaling graphs

Fracture paths in quasi-two-dimensional (2D) media (e.g., thin layers of materials or paper) are analyzed as self-affine graphs h(x) of height h as a function of length x. We show that these are multiscaling, in the sense that nth order moments of the height fluctuations across any distance l scale with a characteristic exponent that depends nonlinearly on the order of the moment. Having demonstrated this, one rules out a widely held conjecture that fracture in 2D belongs to the universality class of directed polymers in random media. In fact, 2D fracture does not belong to any of the known kinetic roughening models. The presence of multiscaling offers a stringent test for any theoretical model; we show that a recently introduced model of quasistatic fracture passes this test.     

Integer valued polynomials and Lubin-Tate formal groups

If R is an integral domain and K is its field of fractions, we let Int(R) stand for the subring of K[x] which maps R into itself. We show that if R is the ring of integers of a p-adic field, then Int(R) is generated, as an R-algebra, by the coefficients of the endomorphisms of any Lubin-Tate group attached to R.     

Superresolved and field-of-view extended digital holography with particle encoding

We present a new configuration for superresolution (SR) as well as for field-of-view (FOV) extension in a digital holography concept based on random movement of sparse metallic particles. In the SR configuration, the particles are in proximity to the recorded object, while in the FOV configuration, the particles are in proximity to the hologram plane. The particles' movement encodes the high spatial features in the plane of their movement. This high-resolution information can later be decoded by proper numerical postprocessing that either remedies the resolution limitations in the object plane (or the limited NA of the lens) or extends the FOV in the object plane.