Laser‐Induced Self‐Assembled Nanostructures on Electron‐Transparent Substrates

Currently, one of the challenges in high‐resolution transmission electron microscopy (TEM) studies of nanomaterials is to make contamination‐free materials in a simple and time‐efficient way. Here, a method is demonstrated that combines nanosecond‐pulsed laser dewetting of thin films with a film float‐off technique to realize nanostructures (NSs) on electron‐transparent substrates in a robust and rapid manner. NSs of metal (Ag) and bimetals (AgCo, AuCo) ranging from 20 to 150 nm are synthesized on thin carbon film deposited on mica substrates. The NS/carbon system is subsequently transferred onto TEM grids by a float‐off process resulting from debonding of the carbon from mica due to their contrasting hydrophobic nature. This process enables the fabrication of different NSs on flexible and electron‐transparent substrates.     

Base mediated synthesis of α-aminated aroyl/acetylnaphthalenes through [4+2] annulations

We have developed a base promoted simple, efficient and alternative approach for the synthesis of 4-amino-3-aroyl//heteroaroyl/acetyl-2-methylsulfanyl-naphthalene-1-carbonitriles by reaction of easily accessible 3,3-bis(methylthio)-1-aryl/heteroaryl/acetylprop-2-en-1-one and 2-cyanomethyl-benzonitrile. Reaction of 1-(2-halo/methoxy-phenyl)-3,3-bis(methylthio)prop-2-en-1-one and 2-cyanomethyl-benzonitrile under basic conditions also afforded 6-(methylthio)-7-oxo-7,12-dihydrobenzo[c]acridine-5-carbonitrile along with usual product. Structure of the synthesized product has been confirmed by single X-ray crystallography.     

A mechanistic study of Protein A chromatography resin lifetime

A mechanistic study into Protein A chromatographic resin lifetime limitations is presented. Binding and mass transport properties of two widely used agarose-based Protein A resins were studied to distinguish between the roles of resin fouling due to product/impurity build-up and ligand degradation as contributory factors towards the decline in binding capacity with use. Cycling studies were conducted with and without product loading on the columns to separate out the influence of resin fouling. Ligand degradation under the mildly alkaline conditions used for column regeneration was determined to be the primary cause for Protein A resin capacity decline with usage. The use of lower concentrations of caustic and the use of stabilizing excipients to protect the Protein A ligand during cleaning and sanitization were found to be useful techniques in maintaining column performance. The results presented in this paper provide a clearer understanding of the causative factors that limit Protein A chromatographic resin lifetime. It is anticipated that these findings will assist in the development of more robust and economical downstream manufacturing processes for monoclonal antibody and Fc fusion protein purification.     

All-atom de novo protein folding with a scalable evolutionary algorithm

The search for efficient and predictive methods to describe the protein folding process at the all-atom level remains an important grand-computational challenge. The development of multi-teraflop architectures, such as the IBM BlueGene used in this study, has been motivated in part by the large computational requirements of such studies. Here we report the predictive all-atom folding of the forty-amino acid HIV accessory protein using an evolutionary stochastic optimization technique. We implemented the optimization method as a master-client model on an IBM BlueGene, where the algorithm scales near perfectly from 64 to 4096 processors in virtual processor mode. Starting from a completely extended conformation, we optimize a population of 64 conformations of the protein in our all-atom free-energy model PFF01. Using 2048 processors the algorithm predictively folds the protein to a near-native conformation with an RMS deviation of 3.43 A in < 24 h.     

Conformational landscape of the HIV-V3 hairpin loop from all-atom free-energy simulations

Small beta hairpins have many distinct biological functions, including their involvement in chemokine and viral receptor recognition. The relevance of structural similarities between different hairpin loops with near homologous sequences is not yet understood, calling for the development of methods for de novo hairpin structure prediction and simulation. De novo folding of beta strands is more difficult than that of helical proteins because of nonlocal hydrogen bonding patterns that connect amino acids that are distant in the amino acid sequence and there is a large variety of possible hydrogen bond patterns. Here we use a greedy version of the basin hopping technique with our free-energy forcefield PFF02 to reproducibly and predictively fold the hairpin structure of a HIV-V3 loop. We performed 20 independent basin hopping runs for 500 cycles corresponding to 7.4 x 10(7) energy evaluations each. The lowest energy structure found in the simulation has a backbone root mean square deviation (bRMSD) of only 2.04 A to the native conformation. The lowest 9 out of the 20 simulations converged to conformations deviating less than 2.5 A bRMSD from native.     

Tetrakis(imidazolyl)borate-based coordination polymers: group II network solids,M[B(Im)4]2(H2O)2 (M = Mg,Ca, Sr)

We are using the coordinating anion tetrakis(imidazolyl)borate to construct new metal-organic framework structures. In this report, we present three alkaline earth metal network solids incorporating this anion. All three compounds have the same formula, M[B(Im)(4)](2)(H(2)O)(2) (M = Mg, Ca, Sr), and the same coordination environment about the metal. However, the three compounds have different network structures with different degrees of hydrogen bonding; the Mg material forms a two-dimensional network and the Ca and Sr compounds form one-dimensional chains. In addition, we present the structure of the protonated anion B(HIm)(Im)(3) as a model for the default structure of this anion and discuss how the conformation of tetrakis(imidazolyl)borate can affect the structure of network solids.