Time-dependent distance restraints in molecular dynamics simulations

A method for enforcing nuclear Overhauser effect (NOE) distance restraints in molecular dynamics simulations is presented. Rather than model the NOE distance as static, a term is included in the force field such that the distance restraint need only be satisfied as a 〈r−3〉−1/3 weighted time average over the simulation trajectory. This provides a better approximation of the physical nature of the NOE and reduces the disturbance to the force field due to the artificial term. Tests on a simple model system demonstrate the inadequacy of current methods and show the advantages of this novel approach, resulting in a more extensive search of conformational spac

Molecular dynamics simulation using weak-coupling NOE distance restraining

Application of the weak-coupling scheme to restrain the configurations of a molecular system to a set of NOE distance restraints is investigated using two test systems: (i) a 15-atom chain molecule with one distance restraint; and (ii) a protein molecule with hundreds of NOE distance restraints. Atom-atom distance restraining by the weak-coupling technique is possible, but this method does not produce as good results as the penalty function method normally used to maintain NOE distance restraints. © 1996 ESCOM Science Publishers B.V

Barreñón

[ES] Definición del término Barreñón en el diccionario Dicter.[EN] Definition of the word Barreñón in the dictionary Dicter

Coupling constants again: Experimental restraints in structure refinement

Utilization of coupling constants as restraints in computational structure refinement is reviewed. In addition, we address the effect of conformational averaging and examine different approaches to apply the restraints when the experimental observable is obviously a result of averaging. Here, two different computational methods are compared. The simulation of a single structure with time-dependent restraints produces results very similar to those obtained with the calculation of numerous copies of the molecule (an ensemble of structures) and ensemble averaging. The advantages and disadvantages of the two methods are illustrated with simulations of cyclosporin A, for which 117 NOEs and 62 homo- and heteronuclear coupling constants have been measured. © 1994 ESCOM Science Publishers B.V

Structure of a stereoregular phosphorothioate DNA/RNA duplex

In this work, we present the first NMR solution structure of a DNA/RNA hybrid containing stereoregular Rp-phosphorothioate modifications of all DNA backbone linkages. The complex of the enzymatically synthesized phosphorothioate DNA octamer (all-R_p)-d(GCGTCAGG) and its complementary RNA r(CCUGACGC) was found to adopt an overall conformation within the A-form family. Most helical parameters and the sugar puckers of the DNA strand assume values intermediate between A- and B-form. The close structural similarity with the unmodified DNA/RNA hybrid of the same sequence may explain why both the natural and the sulfur-substituted complex can be recognized and digested by ribonuclease H