Linear and non-linear aspects of ion cyclotron resonance

A quantum-mechanical approach based on a projection-operator formalism is presented for the ion motion and the instantaneous power absorption in ion cyclotron resonance. The role of non-linearities in the power absorption is investigated by incorporating the formalism in a non-linear response theory, and their effect on the line-shape is discussed.     

Ortho-para hydrogen conversion in paramagnetic solutions

The rate of interconversion of ortho and para hydrogen in a solution of paramagnetic ions is calculated. The rate depends on the correlation of the magnetic fields at the two protons, and this is calculated on the basis of a dipolar interaction modulated by rotational and translational motion of the molecule and the ion. The theory is applied to experimental data on conversion caused by lanthanon and transition metal ions, and is used to estimate the radii of first hydration spheres.     

Molecular dynamics simulation and binding energy calculation for estimation of oligonucleotide duplex thermostability in RNA-based therapeutics

For oligonucleotide-based therapeutics, a thorough understanding of the thermodynamic properties of duplex formation is critical to developing stable and potent drugs. For unmodified small interfering RNA (siRNA), DNA antisense oligonucleotide (AON) and locked nucleic acid (LNA), DNA/LNA modified oligonucleotides, nearest neighbor (NN) methods can be effectively used to quickly and accurately predict duplex thermodynamic properties such as melting point. Unfortunately, for chemically modified olignonucleotides, there has been no accurate prediction method available. Here we describe the potential of estimating melting temperature (T(m)) for nonstandard oligonucleotides by using the correlation of the experimental T(m) with the calculated duplex binding energy (BE) for oligonucleotides of a given length. This method has been automated into a standardized molecular dynamics (MD) protocol through Pipeline Pilot (PP) using the CHARMm component in Discovery Studio (DS). Results will be presented showing the correlation of the predicted data with experiment for both standard and chemically modified siRNA and AON.     

Enhanced macrocyclizing activity of the thioesterase from tyrocidine synthetase in presence of nonionic detergent

Macrocyclization carried out by thioesterase domains of multimodular nonribosomal peptide synthetases (NRPSs) is a key step in the biosynthesis of many biologically active peptides. The thioesterase excised from tyrocidine synthetase is a versatile macrocyclization catalyst and a useful tool for chemoenzymatic synthesis of diverse cyclic peptides. However, its utility is limited by its short lifetime of catalytic activity as well as significant flux of the acyl-enzyme intermediate to hydrolysis. The addition of Brij 58, a nonionic detergent, above the critical micelle concentration, has dramatic effects on enzyme activity: catalytic activity is extended to >60 min and the rate of cyclization (but not hydrolysis) increases 6-fold, resulting in a net 150- to 300-fold increase in cyclic product yields. This enhanced activity allowed enzymatic macrocyclization of a solid phase library of tyrocidine decapeptides to identify acceptable substitutions at the Orn9 position which had previously been inaccessible for diversification.