A flexible docking procedure for the exploration of peptide binding selectivity to known structures and homology models of PDZ domains

PDZ domains are important scaffolding modules that typically bind to the C-termini of their interaction partners. Several structures of such complexes have been solved, revealing a conserved binding site in the PDZ domain and an extended conformation of the bound peptide. A compendium of information regarding PDZ complexes demonstrates that dissimilar C-terminal peptides bind to the same PDZ domain, and different PDZ domains can bind the same peptides. A detailed understanding of the PDZ-peptide recognition is needed to elucidate this complexity. To this end, we have designed a family of docking protocols for PDZ domains (termed PDZ-DocScheme) that is based on simulated annealing molecular dynamics and rotamer optimization, and is applicable to the docking of long peptides (20-40 rotatable bonds) to both known PDZ structures and to the more complicated problem of homology models of these domains. The resulting protocol reproduces the structures of PDZ complexes with peptides 4-8 amino acids long within 1-2 A from the experimental structure when the docking is performed to the original structure. If the structure of the target PDZ domain is an apo structure or a homology model, the docking protocol yields structures within 3 A in 9 out of 12 test cases. The automated docking procedure PDZ-DocScheme can serve in the generation of a structural context for validation of PDZ domain specificity from mutagenesis and ligand binding data.     

Reversible photomechanical switching of individual engineered molecules at a metallic surface

We have observed reversible light-induced mechanical switching for individual organic molecules bound to a metal surface. Scanning tunneling microscopy (STM) was used to image the features of individual azobenzene molecules on Au(111) before and after reversibly cycling their mechanical structure between trans and cis states using light. Azobenzene molecules were engineered to increase their surface photomechanical activity by attaching varying numbers of tert-butyl (TB) ligands ("legs") to the azobenzene phenyl rings. STM images show that increasing the number of TB legs "lifts" the azobenzene molecules from the substrate, thereby increasing molecular photomechanical activity by decreasing molecule-surface coupling.     

Formation of helical beams by use of Pancharatnam-Berry phase optical elements

Spiral phase elements with topological charges based on space-variant Pancharatnam-Berry phase optical elements are presented. Such elements can be achieved by use of continuous computer-generated space-variant subwavelength dielectric gratings. We present a theoretical analysis and experimentally demonstrate spiral geometrical phases for infrared radiation at a wavelength of 10.6microm .     

Formation of novel rare-gas-containing molecules by molecular photodissociation in clusters

Recent work by R?s?nen and coworkers showed that photolysis of hydrides in rare-gas matrices results in part in formation of novel, rare-gas-containing molecules. Thus, photolysis of HCl in Xe and of H2O in Xe result respectively in formation of HXeCl and HXeOH in the Xe matrices. Ab initio calculations show that the compounds HRgY so formed are stable in isolation, and that by the strength and nature of the bonding these are molecules, very different from the corresponding weakly bound clusters Rg...HY. This paper presents a study of the formation mechanism of HRgY following the photolysis of HY in clusters Rgn(HY). Calculations are described for HXeCl, as a representative example. Potential energy surfaces that govern the formation of HXeCl in the photolysis of HCl in xenon clusters are obtained, and the dynamics on these surfaces is analyzed, partly with insight from trajectories of molecular dynamics simulations. The potential surfaces are obtained by a new variant of the DIM (diatomics in molecules) and DIIS (diatomics in ionic systems) models. Non-adiabatic couplings are also obtained. The main results are: (1) Properties of HXeCl predicted by the DIM-DIIS model are in reasonable accord with results of ab initio calculations. (2) The potential along the isomerization path HXeCl-->Xe...HCl predicted by DIM is in semiquantitative accord with the ab initio results. (3) Surface-hopping molecular dynamics simulations of the process in clusters, with "on the fly" calculations of the DIM-DIIS potentials and non-adiabatic couplings are computationally feasible. (4) Formation of HXeCl, following photolysis of HCl in Xe54(HCl), requires cage-exit of the H atom as a precondition. The H atom and the Cl can then attack the same Xe atom on opposite sides, leading to charge transfer and production of the ionic HXeCl. (5) Non-adiabatic processes play an important role, both in the reagent configurations, and at the charge-transfer stage. The results open the way to predictions of the formation of new HRgY species.     

Observation of the spin-based plasmonic effect in nanoscale structures

Observation of surface-plasmon phenomena that are dependent upon the handedness of the circularly polarized incident light (spin) is presented. The polarization-dependent near-field intensity distribution obtained in our experiment is attributed to the presence of a geometric phase arising from the interaction of light with an anisotropic and inhomogeneous nanoscale structure. A near-field vortex surface mode with a spin-dependent topological charge was obtained in a plasmonic microcavity. The remarkable phenomenon of polarization-sensitive focusing in a plasmonic structure was also demonstrated.     

Expression and Structure/Function Relationships of Human Defensin 5

The innate immunity utilizes a battery of broad-spectrum antibacterial cationic polypeptides (3–5 kDa), among them defensins. In humans, defensins are the first line of defense against pathogens and their expression has been implicated in several diseases. The antibacterial activity of defensins is generally ascribed to their overall positive charge, which enables them to disrupt bacterial membrane integrity and function, but their active surface has not been fully elucidated. To perform structural and functional assays, an efficient, high-yield, easy-to-use expression and purification system must be established. Up to now, most efforts to obtain larger quantities of active recombinant defensins have been only moderately successful. Herein, we report the establishment of an efficient, high-yield expression and purification system for human defensin 5 (HD-5). Using site-directed mutagenesis, we pinpoint several arginine residues and Y27 as important for HD-5 antibacterial activity. Our expression and purification system can be harnessed for structure/activity relationship studies of defensins in particular and small polypeptides in general.     

Nuclear polarization generated in multi tilted-foil arrays

I first met Kenzo Sugimoto in 1957 at MIT and at theg factor of the 2⁺ state in¹⁵²Sm — a crossroad of nuclear and atomic physics. After that our ways diverged until they came together again half a lifetime later at another crossroad and another playfield — the tilted-foil nuclear polarization. I submit here for his pleasure, together with my colleague Yehuda Niv, a glimpse into the mysteries of multi-foil assemblies.Supported in part by the National Science Foundation.     

Devising a Cooperation Policy for Emergency Networks

A mathematical programming model is proposed to select an optimal cooperation policy between autonomous service networks for dispatching purposes. In addition to traditional characteristics such as network topology and station location, this model takes into account 'political' constraints on minimum response-time in certain subzones. Such constraints are translated into performance requirements, which are imposed on the cooperation policy. Testing the model under different assumptions can be useful for analysing various cooperation policies. The paper formulates a mathematical programming model, derives example policies for various circumstances, and tests the sensitivity of the resultant policies to some parameters, such as the penalty for not providing service, and distances between adjacent networks. The paper suggests also a less constrained approach, which entails a linear programming model. A comparison between the two approaches is presented.