6VLU

Factor XIa in complex with compound 7


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.203 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Augmenting Hit Identification by Virtual Screening Techniques in Small Molecule Drug Discovery.

Yan, X.C.Sanders, J.M.Gao, Y.D.Tudor, M.Haidle, A.M.Klein, D.J.Converso, A.Lesburg, C.A.Zang, Y.Wood, H.B.

(2020) J Chem Inf Model 60: 4144-4152

  • DOI: https://doi.org/10.1021/acs.jcim.0c00113
  • Primary Citation of Related Structures:  
    6VLM, 6VLU, 6VLV

  • PubMed Abstract: 

    Two orthogonal approaches for hit identification in drug discovery are large-scale in vitro and in silico screening. In recent years, due to the emergence of new targets and a rapid increase in the size of the readily synthesizable chemical space, there is a growing emphasis on the integration of the two techniques to improve the hit finding efficiency. Here, we highlight three examples of drug discovery projects at Merck & Co., Inc., Kenilworth, NJ, USA in which different virtual screening (VS) techniques, each specifically tailored to leverage knowledge available for the target, were utilized to augment the selection of high-quality chemical matter for in vitro assays and to enhance the diversity and tractability of hits. Central to success is a fully integrated workflow combining in silico and experimental expertise at every stage of the hit identification process. We advocate that workflows encompassing VS as part of an integrated hit finding plan should be widely adopted to accelerate hit identification and foster cross-functional collaborations in modern drug discovery.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Coagulation factor XIa light chain238Homo sapiensMutation(s): 1 
Gene Names: F11
EC: 3.4.21.27
UniProt & NIH Common Fund Data Resources
Find proteins for P03951 (Homo sapiens)
Explore P03951 
Go to UniProtKB:  P03951
PHAROS:  P03951
GTEx:  ENSG00000088926 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03951
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
R2Y (Subject of Investigation/LOI)
Query on R2Y

Download Ideal Coordinates CCD File 
C [auth A]N-cyclohexyl-D-leucyl-N-[(1-aminoisoquinolin-6-yl)methyl]-4,4-difluoro-L-prolinamide
C27 H37 F2 N5 O2
COYOMWYNPNKVLE-PKTZIBPZSA-N
CIT
Query on CIT

Download Ideal Coordinates CCD File 
B [auth A]CITRIC ACID
C6 H8 O7
KRKNYBCHXYNGOX-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
R2Y Binding MOAD:  6VLU Ki: 149.1 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.201 
  • R-Value Observed: 0.203 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 59.126α = 90
b = 59.886β = 90
c = 68.018γ = 90
Software Package:
Software NamePurpose
d*TREKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
BUSTERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-05-06
    Type: Initial release
  • Version 1.1: 2020-10-07
    Changes: Database references