Data processing: measuring – calibrating – or testing – Measurement system – Dimensional determination
Reexamination Certificate
2011-06-28
2011-06-28
Le, John H (Department: 2857)
Data processing: measuring, calibrating, or testing
Measurement system
Dimensional determination
C702S019000, C702S027000, C702S136000, C374S045000
Reexamination Certificate
active
07970580
ABSTRACT:
Described is a technique to exhaustively enumerate the thermodynamic properties of the water molecules solvating the active site of a protein in its apostate and calculate the relative binding affinities of congeneric compounds that bind to this protein. The subject matter includes sampling the configurations of the solvating water in the active site; extracting the thermodynamic information about the solvating water from these configurations by clustering the observed water configurations into regions of high water occupancy (e.g., “hydration sites”), computing the average system interaction energies of water molecules occupying the various hydrations sites, computing excess entropies of water molecules occupying the hydration sites; constructing a 3 dimensional hydration thermodynamics map of the protein active site; and computing relative binding affinities of congeneric ligands based on the principle that tighter binding ligands can displace more entropically structured and energetically depleted hydration sites from the active site into the bulk fluid.
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Abel Robert
Berne Bruce J.
Friesner Richard A.
Young Thomas
Baker & Botts LLP
Le John H
The Trustees of Columbia University in the City of New York
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