Abstract: Described herein is technology for determining the 2-D or 3-D atomic resolution structure of a polynucleotide bound to and/or interacting with another molecule, for example a small molecule. In some aspects of the technology, NMR and isotopic labeling strategies are used. The technology described herein is useful for a plurality of applications including but not limited to drug discovery and chemical biology probe discovery.

Abstract: The present invention provides a method for determining the 3-dimensional or 3-D atomic resolution structure of a biomolecule using chemical shift data obtained from the biomolecule having one or more selectively isotopically labeled biomolecule monomers and interrogation of same using an NMR device. Methods also comprise use of a low-field NMR device and structure determination method to determine the 2-D and 3-D structure of the biomolecule, for example, a polynucleotide.

Abstract: Described herein is technology for determining the 2-D or 3-D atomic resolution structure of a polynucleotide bound to and/or interacting with another molecule, for example a small molecule. In some aspects of the technology, NMR and isotopic labeling strategies are used. The technology described herein is useful for a plurality of applications including but not limited to drug discovery and chemical biology probe discovery.

Abstract: The present invention provides a method for determining the 3-dimensional or 3-D atomic resolution structure of a biomolecule using chemical shift data obtained from the biomolecule having one or more selectively isotopically labeled biomolecule monomers and interrogation of same using an NMR device. Methods also comprise use of a low-field NMR device and structure determination method to determine the 2-D and 3-D structure of the biomolecule, for example, a polynucleotide.

Abstract: Methods for generating putative ligand structures capable of altering the activity of a target effector molecule comprise: constructing an elongated monomer of the target effector molecule; constructing a three dimensional model of the target effector molecule under the influence of elongation using empirical three dimensional data, the model including a conformation revealing the binding portion of the target effector molecule to a putative ligand structure; generating a plurality of computational models of the target effector molecule; filtering the plurality of computational models against the three dimensional model created experimentally using a reiterative simulation analysis algorithm operable to identify and select a plurality of computational models having a root-mean square deviation below a predetermined threshold when compared to the three dimensional model of the target effector molecule; screening a plurality of ligands to rank the binding strength of each ligand with the plurality of computatio

Abstract: Methods for generating putative ligand structures capable of altering the activity of a target effector molecule comprise: constructing an elongated monomer of the target effector molecule; constructing a three dimensional model of the target effector molecule under the influence of elongation using empirical three dimensional data, the model including a conformation revealing the binding portion of the target effector molecule to a putative ligand structure; generating a plurality of computational models of the target effector molecule; filtering the plurality of computational models against the three dimensional model created experimentally using a reiterative simulation analysis algorithm operable to identify and select a plurality of computational models having a root-mean square deviation below a predetermined threshold when compared to the three dimensional model of the target effector molecule; screening a plurality of ligands to rank the binding strength of each ligand with the plurality of computatio

Abstract: Methods of using NMR spectroscopy for identifying ligands that bind to structurally uncharacterized proteins, and improving the binding affinity of ligands for biological targets are disclosed. One aspect of the method includes preparing first NMR spectra of a first complex comprising the biological target and a paramagnetically labeled derivative of a first ligand, preparing a second NMR spectra of a second complex comprising the biological target and a second ligand, and analyzing the spectra to determine whether the second ligand binds to the biological target within the paramagnetic zone of the paramagnetically labeled derivative. The first and second steps may be performed simultaneously, consecutively, or in any order.

Abstract: Methods of using NMR spectroscopy for identifying ligands that bind to structurally uncharacterized proteins, and for improving the binding affinity of ligands for biological targets, which in one aspect comprises: