6BKW

BTK complex with compound 12


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.190 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.164 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Water molecules in protein-ligand interfaces. Evaluation of software tools and SAR comparison.

Nittinger, E.Gibbons, P.Eigenbrot, C.Davies, D.R.Maurer, B.Yu, C.L.Kiefer, J.R.Kuglstatter, A.Murray, J.Ortwine, D.F.Tang, Y.Tsui, V.

(2019) J Comput Aided Mol Des 33: 307-330

  • DOI: https://doi.org/10.1007/s10822-019-00187-y
  • Primary Citation of Related Structures:  
    6BIK, 6BKE, 6BKH, 6BKW, 6BLN, 6BQA, 6BQD, 6EP9

  • PubMed Abstract: 

    Targeting the interaction with or displacement of the 'right' water molecule can significantly increase inhibitor potency in structure-guided drug design. Multiple computational approaches exist to predict which waters should be targeted for displacement to achieve the largest gain in potency. However, the relative success of different methods remains underexplored. Here, we present a comparison of the ability of five water prediction programs (3D-RISM, SZMAP, WaterFLAP, WaterRank, and WaterMap) to predict crystallographic water locations, calculate their binding free energies, and to relate differences in these energies to observed changes in potency. The structural cohort included nine Bruton's Tyrosine Kinase (BTK) structures, and nine bromodomain structures. Each program accurately predicted the locations of most crystallographic water molecules. However, the predicted binding free energies correlated poorly with the observed changes in inhibitor potency when solvent atoms were displaced by chemical changes in closely related compounds.


  • Organizational Affiliation

    Universität Hamburg, ZBH - Center for Bioinformatics, Bundesstraße 43, 20146, Hamburg, Germany. nittinger@zbh.uni-hamburg.de.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase BTK287Homo sapiensMutation(s): 0 
Gene Names: BTKAGMX1ATKBPK
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for Q06187 (Homo sapiens)
Explore Q06187 
Go to UniProtKB:  Q06187
PHAROS:  Q06187
GTEx:  ENSG00000010671 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ06187
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DXM (Subject of Investigation/LOI)
Query on DXM

Download Ideal Coordinates CCD File 
E [auth A]N-(3-{5-[(1,5-dimethyl-1H-pyrazol-3-yl)amino]-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl}-2,6-difluorophenyl)-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide
C25 H24 F2 N6 O2 S
CAJCMVSBNVIKHV-UHFFFAOYSA-N
FPZ
Query on FPZ

Download Ideal Coordinates CCD File 
F [auth A]triphenylphosphane
C18 H15 P
RIOQSEWOXXDEQQ-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A],
D [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
G [auth A],
H [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
OCS
Query on OCS
A
L-PEPTIDE LINKINGC3 H7 N O5 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.190 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.164 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 108.765α = 90
b = 108.765β = 90
c = 41.863γ = 120
Software Package:
Software NamePurpose
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-11-07
    Type: Initial release
  • Version 1.1: 2019-02-27
    Changes: Data collection, Database references
  • Version 1.2: 2019-03-27
    Changes: Data collection, Database references