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

US8498823B2 · kind B2 · utility

Assignee

• THE REGENTS OF THE UNIVERSITY OF MICHIGAN · US

Inventors

• Hashim M. Al-Hashimi · Ann Arbor, US
• Andrew Corbet Stelzer · Ann Arbor, US
• Ioan Andricioaei · Irvine, US
• Aaron Frank · Irvine, US

Key dates

• Filing date: Sep 25, 2009
• Grant date: Jul 30, 2013
• Expiry date: Sep 25, 2029

Classification

• Technology area (CPC G): Physics
• CPC primary: G16B20/00
• WIPO field: Measurement
• WIPO sector: Instruments

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