Tightening up the structure,lighting up the pathway: application of molecular constraints and light to manipulate protein folding,self-assembly and function

Chemical cross-linking provides an effective avenue to reduce the conformational entropy of polypeptide chains and hence has become a popular method to induce or force structural formation in peptides and proteins.Recently,other types of molecular constraints,especially photoresponsive linkers and functional groups,have also found increased use in a wide variety of applications.Herein,we provide a concise review of using various forms of molecular strategies to constrain proteins,thereby stabilizing their native states,gaining insight into their folding mechanisms,and/or providing a handle to trigger a conformational process of interest with light.The applications discussed here cover a wide range of topics,ranging from delineating the details of the protein folding energy landscape to controlling protein assembly and function.     

Electron impact mass spectrometry of some benzodioxole derivatives of pharmacological interest,their synthons and synthetic intermediates

The mass spectrometric behaviour of two newly synthesized β-blocking benzodioxole derivatives, their synthons and synthetic intermediates has been studied in detail with the aid of exact mass measurements, linked scans, collisionally activated decomposition mass analysed ion kinetic energy spectra and deuterium labelling experiments. A retrosynthetic process, leading to the original synthons, is described.     

Two-level primal-dual decomposition technique for large-scale nonconvex optimization problems with constraints

A two-level decomposition method for nonconvex separable optimization problems with additional local constraints of general inequality type is presented and thoroughly analyzed in the paper. The method is of primal-dual type, based on an augmentation of the Lagrange function. Previous methods of this type were in fact three-level, with adjustment of the Lagrange multipliers at one of the levels. This level is eliminated in the present approach by replacing the multipliers by a formula depending only on primal variables and Kuhn-Tucker multipliers for the local constraints. The primal variables and the Kuhn-Tucker multipliers are together the higher-level variables, which are updated simultaneously. Algorithms for this updating are proposed in the paper, together with their convergence analysis, which gives also indications on how to choose penalty coefficients of the augmented Lagrangian. Finally, numerical examples are presented.     

Density functional studies of the dipole polarizabilities of the linear polyacenes benzene through nonacene

We report Ab Initio studies of the electric dipole polarizability of the linear polyacene series benzene through nonacene. A number of Ab Initio studies were done at different levels of theory for benzene, with all remaining Ab Initio calculations being at the B3LYP/6-311G(2d, 1p)//B3LYP/6-311+G(2d, 1p) level of theory. We find that the NN tensor component shows a constant increment of 20 atomic units per ring. AM1 and QSAR-quality empirical calculations show poor absolute agreement with the Ab Initio results but given excellent statistical correlation coefficients with the Ab Initio values. This implies that the results of such cheaper calculations can be suitably scaled for predictive purposes.     

Transmission of spin—spin coupling constants through different paths in bicyclo(2,2,1)heptane: their calculation using inner projections of the polarization propagator

Inner projections of the polarization propagator are used to calculate components of the Fermi contact interaction between protons attached to the bridgehead carbon atoms of bicyclo(2,2,1)Heptane. Four- and five-bond paths and throuh-space interaction are considered. Reasonable path additivity and agreement with experimental data are found at the INDO level.     

Influence of the INDO parameterization on the indirect spin–spin coupling constants as calculated by the FPT INDO method

Alterations have been introduced in the semi-empirical INDO parameters in order to study their influence on the Fermi contact term of the indirect spin–spin coupling constants as calculated by the finite perturbation theory (FPT). For this purpose a set of molecules containing hydrogen, carbon and/or fluorine has been selected. In general, most coupling constants are found to be much more sensitive than other molecular properties to small changes in the INDO parameters. This sensitivity depends strongly on the particular calculated coupling constant. In most cases the uncertainty in the INDO parameters leads to uncertainties in the coupling constants which are much greater than their experimental errors.