University of Michigan

Nymirum, Inc.

Other

Hashim M Al-Hashimi

Andrew Corbet Stelzer

Sung-Hun Bae

Jeanne Stuckey

David M Markovitz

Jennifer Lynn Meagher

Michael Edward Pape

James H Prestegard

Andre P Venot

Laura C Morris

Nitin U Jain

Aaron Frank

Ioan Andricioaei

Joshua Paul Fairbank

Aaron Terrence Frank

Loic Salmon

Daniel M Boudreaux

Mitchell Alan McBrairty

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.

Small molecule binding pockets in nucleic acids

Provided herein are chemical compounds, methods for their discovery, and their therapeutic and research use. Further provided herein are antiviral and antimicrobial lectin compounds and methods of their use.

Lectins and uses thereof

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.

Device and methods for analysis of biomolecule structure, dynamics and activity

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 computational models selected and selecting one or more ligands based on the ranking.

High-throughput ensemble-based docking and elucidation of 3-dimensional structural conformations of flexible biomolecular targets

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.

NMR assisted design of high affinity ligands for structurally uncharacterized proteins

Growing community of inventors

Ann Arbor, MI, United States of America

Hashim M Al-Hashimi