Timothy A Cross

US Patent:

7674595, Mar 9, 2010

Filed:

Feb 5, 2009

Appl. No.:

12/366173

Inventors:

Timothy A. Cross - Tallahassee FL, US
William W. Brey - Tallahassee FL, US
Alexej Smirnov - Raleigh NC, US
Eduard Y. Chekmenev - Pasadena CA, US

Assignee:

The Florida State University Research Foundation, Inc. - Tallahassee FL

International Classification:

G01N 33/53

US Classification:

435 71, 4352831, 436501, 436518, 422 50, 257 9

Abstract:

Disclosed is a method for detection of ligand-cell membrane protein binding by solid state NMR spectroscopy. The method starts by forming a lipid bilayer inside nanopores of an anodic aluminum oxide (AAO) substrate, the lipid bilayer containing a membrane protein sample. The AAO substrate is treated with multiple candidate ligands having potential binding affinity for the membrane protein. Solid-state NMR analysis is performed on the treated AAO/lipid preparation so as to generate an NMR spectrum for the treated membrane protein. The solid-state NMR spectrum of the treated membrane protein is compared with the spectrum of the same preparation of membrane protein in the absence of the ligands. It is then determined whether the solid-state NMR spectrum of the treated membrane protein has shifted from the NMR spectrum of the untreated membrane protein, a shift being indicative of protein binding by the candidate ligand.

US Patent:

7678546, Mar 16, 2010

Filed:

Oct 1, 2007

Appl. No.:

11/865302

Inventors:

Timothy Cross - Tallahassee FL, US
William W. Brey - Tallahassee FL, US
Alexej Smirnov - Raleigh NC, US
Eduard Y Chekmenev - Pasadena CA, US

Assignee:

The Florida State University Research Foundation, Inc. - Tallahassee FL

International Classification:

G01N 33/53

US Classification:

435 71, 4352831, 436501, 436518, 422 50, 257 9

Abstract:

Disclosed is a method for detection of ligand-cell membrane protein binding by solid state NMR spectroscopy. The method starts by forming a lipid bilayer inside nanopores of an anodic aluminum oxide (AAO) substrate, the lipid bilayer containing a membrane protein sample. The AAO substrate is treated with multiple candidate ligands having potential binding affinity for the membrane protein. Solid-state NMR analysis is performed on the treated AAO/lipid preparation so as to generate an NMR spectrum for the treated membrane protein. The solid-state NMR spectrum of the treated membrane protein is compared with the spectrum of the same preparation of membrane protein in the absence of the ligands. It is then determined whether the solid-state NMR spectrum of the treated membrane protein has shifted from the NMR spectrum of the untreated membrane protein, a shift being indicative of protein binding by the candidate ligand.

US Patent:

7754438, Jul 13, 2010

Filed:

Feb 5, 2009

Appl. No.:

12/366190

Inventors:

Timothy Cross - Tallahassee FL, US
William W. Brey - Tallahassee FL, US
Alexej Smirnov - Raleigh NC, US
Eduard Y. Chekmenev - Pasadena CA, US

Assignee:

The Florida State University Research Foundation, Inc. - Tallahassee FL

International Classification:

G01N 33/53

US Classification:

435 71, 4352831, 436501, 436518, 422 50, 257 9

Abstract:

Disclosed is a method for detection of ligand-cell membrane protein binding by solid state NMR spectroscopy. The method starts by forming a lipid bilayer inside nanopores of an anodic aluminum oxide (AAO) substrate, the lipid bilayer containing a membrane protein sample. The AAO substrate is treated with multiple candidate ligands having potential binding affinity for the membrane protein. Solid-state NMR analysis is performed on the treated AAO/lipid preparation so as to generate an NMR spectrum for the treated membrane protein. The solid-state NMR spectrum of the treated membrane protein is compared with the spectrum of the same preparation of membrane protein in the absence of the ligands. It is then determined whether the solid-state NMR spectrum of the treated membrane protein has shifted from the NMR spectrum of the untreated membrane protein, a shift being indicative of protein binding by the candidate ligand.

US Patent:

8581584, Nov 12, 2013

Filed:

May 26, 2011

Appl. No.:

13/067351

Inventors:

Mukesh Sharma - Tallahassee FL, US
Myunggi Yi - Busan, KR
Hao Dong - Tallahassee FL, US
Huajun Qin - Tallahassee FL, US
David D. Busath - Orem UT, US
Timothy A. Cross - Tallahassee FL, US

Assignee:

Florida State University Research Foundation - Tallahassee FL

International Classification:

G01V 3/00

US Classification:

324309, 324300

Abstract:

The invention relates to the atomistic functional understanding of the M2 protein from the influenza A virus. This acid-activated selective proton channel has been the subject of numerous conductance, structural, and computational studies. Previously, little was known at the atomic level about the heart of the functional mechanism of this tetrameric protein, a tetrad of HxxxW residues. The structure of the M2 conductance domain in a lipid bilayer is disclosed and displays the defining features of the native protein that have not been attainable from structures solubilized by detergents. A detailed mechanism for acid activation and proton conductance, involving a strong hydrogen bond between two adjacent histidines and specific interactions with the tryptophan gate, is provided and elucidates many observations on the M2 proton conductance.