NMR paper Identifying protein allosteric transitions for drug discovery using 1D NMR.

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[NMR paper] Identifying protein allosteric transitions for drug discovery using 1D NMR.

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NMR processing:

MDD

NMR assignment:

Backbone:

Side-chains:

NOEs:

Structure from NMR restraints:

Ab initio:

Fragment-based:

Rosetta-NMR (Robetta)

Template-based:

GeNMR

I-TASSER

Refinement:

Amber

Structure from chemical shifts:

Fragment-based:

Homology-based:

Torsion angles from chemical shifts:

Preditor

TALOS

Promega- Proline

Secondary structure from chemical shifts:

CSI (via RCI server)

TALOS

MICS caps, β-turns

d2D

PECAN

Flexibility from chemical shifts:

RCI

Interactions from chemical shifts:

HADDOCK

Chemical shifts re-referencing:

NMR model quality:

NOEs, other restraints:

Chemical shifts:

RDCs:

Pseudocontact shifts:

Protein geomtery:

SAVES2 or SAVES4

Quality Control Check

NMR spectrum prediction:

FANDAS

MestReS

V-NMR

Flexibility from structure:

Backbone S2

Methyl S2

B-factor

Molecular dynamics:

Gromacs

Amber

Antechamber

Chemical shifts prediction:

From structure:

Shiftx2

Sparta+

Camshift

CH3shift- Methyl

ArShift- Aromatic

ShiftS

Proshift

PPM

CheShift-2- Cα

From sequence:

Shifty

Camcoil

Poulsen_rc_CS

Disordered proteins:

MAXOCC

Format conversion & validation:

CCPN

From NMR-STAR 3.1

Validate NMR-STAR 3.1

NMR sample preparation:

Protein disorder:

DisMeta

Protein solubility:

Isotope labeling:

Solid-state NMR:

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03-07-2017, 08:54 PM

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Identifying protein allosteric transitions for drug discovery using 1D NMR.

Identifying protein allosteric transitions for drug discovery using 1D NMR.

Related Articles Identifying protein allosteric transitions for drug discovery using 1D NMR.

ChemMedChem. 2017 Mar 06;:

Authors: Krimm I

Abstract
Allosteric drugs present many advantages over orthosteric drugs and represent therefore an attractive approach in drug discovery, yet highly challenging. First, the binding of ligands in protein allosteric pockets do not ensure allosteric effect and second, allosteric ligands can possess diverse modes of pharmacology even within a compound family. Here we report a new method (1) to detect allosteric communication between protein binding sites and (2) to compare the effect of allosteric ligands on the allosteric transitions of the protein target. The method, illustrated with the Glycogen Phosphorylase protein, consists in comparing 1D NMR STD spectra of a molecule spy (here fragments) in the absence and presence of allosteric ligands. The modification of the STD spectrum of the fragment indicates whether the protein dynamics/conformations have been changed in the presence of the allosteric modulator, therefore highlighting allosteric coupling between the binding pocket of the reference compound (here the fragment) and the allosteric pocket.

PMID: 28263035 [PubMed - as supplied by publisher]

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