Robert E Abel

US Patent:

7756674, Jul 13, 2010

Filed:

Nov 5, 2007

Appl. No.:

11/982783

Inventors:

Thomas Young - New York NY, US
Robert Abel - Davie FL, US
Richard A. Friesner - New York NY, US
Bruce J. Berne - Irvington NY, US

Assignee:

The Trustees of Columbia University in the City of New York - New York NY

International Classification:

G06F 17/18
G01N 33/53

US Classification:

702172, 702 19, 702 27, 702179

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.

US Patent:

7970580, Jun 28, 2011

Filed:

Jun 1, 2010

Appl. No.:

12/791448

Inventors:

Thomas Young - New York NY, US
Robert Abel - Davie FL, US
Richard A. Friesner - New York NY, US
Bruce J. Berne - Irvington NY, US

Assignee:

The Trustees of Columbia University in the City of New York - New York NY

International Classification:

G01N 33/48

US Classification:

702172, 702 19, 702 27, 702136, 374 45

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.

US Patent:

7970581, Jun 28, 2011

Filed:

Jun 1, 2010

Appl. No.:

12/791493

Inventors:

Thomas Young - New York NY, US
Robert Abel - Davie FL, US
Richard A. Friesner - New York NY, US
Bruce J. Berne - Irvington NY, US

Assignee:

The Trustees of Columbia University in the City of New York - New York NY

International Classification:

G01N 33/48

US Classification:

702172, 702 19, 702 27, 702136, 374 45

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.

US Patent:

20210035660, Feb 4, 2021

Filed:

Jul 15, 2020

Appl. No.:

16/929591

Inventors:

- New York NY, US
Yuqing Deng - New York NY, US
Yujie Wu - New York NY, US
Byungchan Kim - West New York NJ, US
Robert L. Abel - Brooklyn NY, US

International Classification:

G16C 20/50
G16B 15/00
G16B 15/30

Abstract:

A method for computing free energy difference between a reference molecule and a target molecule. The target molecule has the common set of atoms Pand a set of atoms P. The method includes applying a potential to restrain an interaction of the additional atomic component from the set of atoms Pwith the common set of atoms Pin the initial state. The method includes determining one or more transition states along a transformation path between the initial state and target state. The method includes scaling the restrain potential correspondingly along the transformation path until the potential becomes zero when a corresponding end state is reached, and calculating the free energy difference between the reference molecule and the target molecule using a value obtained along the transformation path from the initial state to the target state.

US Patent:

20190237165, Aug 1, 2019

Filed:

Feb 4, 2019

Appl. No.:

16/267085

Inventors:

- New York NY, US
Robert L. Abel - Brooklyn NY, US

International Classification:

G16C 20/30
G06F 17/50

Abstract:

Methods of calculating a free energy of solubility for a compound in a solvent by computer operations include the following steps: (i) establishing, using a computer model, an initial state for a system including an aggregate of multiple molecules of the compound in a solvent; (ii) establishing, using the computer model, a final state of the system including a single molecule from the aggregate fully solvated in the solvent and separate from a transformed aggregate; (iii) transforming, using the computer model, the system from the initial state to the final state, via removing a first molecule of the compound from the aggregate to form the transformed aggregate and replacing the first molecule with solvent at the site of the first molecule; and (iv) calculating the free energy of the transformation between the initial and the final states, which determines the free energy of solubility for the compound.

US Patent:

20190065697, Feb 28, 2019

Filed:

Aug 22, 2017

Appl. No.:

15/683678

Inventors:

- New York NY, US
Yuqing Deng - New York NY, US
Yujie Wu - New York NY, US
Byungchan Kim - West New York NJ, US
Robert Abel - Brooklyn NY, US

International Classification:

G06F 19/00
G06F 19/16

Abstract:

A method for computing free energy difference between a reference molecule and a target molecule. The target molecule has the common set of atoms Pand a set of atoms P. The method includes applying a potential to restrain an interaction of the additional atomic component from the set of atoms Pwith the common set of atoms Pin the initial state. The method includes determining one or more transition states along a transformation path between the initial state and target state. The method includes scaling the restrain potential correspondingly along the transformation path until the potential becomes zero when a corresponding end state is reached, and calculating the free energy difference between the reference molecule and the target molecule using a value obtained along the transformation path from the initial state to the target state.

US Patent:

20190026423, Jan 24, 2019

Filed:

Jul 25, 2018

Appl. No.:

16/045366

Inventors:

- New York NY, US
Teng Lin - Manalapan NJ, US
Robert L. Abel - Brooklyn NY, US

International Classification:

G06F 19/16
G06F 19/00

Abstract:

Methods for assessing the consistency and reliability of the calculations using cycle closures in relative binding free energy calculation paths. The methods are used for determining relative strength of binding between a receptor and individual members of a set ligands to form complexes between individual ligand set members and the receptor, in which the binding free energy difference with the lowest error is determined by probabilistic determination of the free energy differences and error distributions about those differences along each of the legs of the closed thermodynamic cycle that probabilistically lead to the hysteresis(es) value(s) observed for each closed of the closed thermodynamic cycle.

US Patent:

20160321432, Nov 3, 2016

Filed:

Apr 29, 2016

Appl. No.:

15/142178

Inventors:

- New York NY, US
Robert Abel - Brooklyn NY, US

International Classification:

G06F 19/00
G06F 17/18

Abstract:

Methods of calculating a free energy of solubility for a compound in a solvent by computer operations include the following steps: (i) establishing, using a computer model, an initial state for a system including an aggregate of multiple molecules of the compound in a solvent; (ii) establishing, using the computer model, a final state of the system including a single molecule from the aggregate fully solvated in the solvent and separate from a transformed aggregate; (iii) transforming, using the computer model, the system from the initial state to the final state, via removing a first molecule of the compound from the aggregate to form the transformed aggregate and replacing the first molecule with solvent at the site of the first molecule; and (iv) calculating the free energy of the transformation between the initial and the final states, which determines the free energy of solubility for the compound.

Author:

Robert B. Abel

ISBN #:

0444015604

Author:

Robert B. Abel

ISBN #:

0761806989

Author:

Robert B. Abel

ISBN #:

0761806997

Author:

Robert Abel

ISBN #:

0671509314

Author:

Robert Abel

ISBN #:

0758202199

Author:

Robert Abel

ISBN #:

0758206224

Author:

Robert H. Abel

ISBN #:

0820312525