comparing acedrg vs csd · • run refmac5 to assess geometry (idealisation mode) compare with csd...

Comparing AceDRG vs CSD

LIGANDS Meeting Sept 2017

Rob Nicholls nicholls@mrc-lmb.cam.ac.uk

1

AceDRG vs CSDSuggested by Oliver Smart

Monomer library update CCD entries in the CSD

323 5073 1517

2

3

AceDRG vs CSD323 Comp IDs from the CCD

Establish Baseline – original PDB files:•  Take PDBs•  Extract ligand coordinates•  Run REFMAC5 to assess geometry (idealisation mode)

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AceDRG vs CSD323 Comp IDs from the CCD

Establish Baseline – original PDB files:•  Take PDBs•  Extract ligand coordinates•  Run REFMAC5 to assess geometry (idealisation mode)

Re-refined PDB using AceDRG dictionary (monomer library update)•  Extract ligand coordinates•  Run REFMAC5 to assess geometry (idealisation mode)

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AceDRG vs CSD323 Comp IDs from the CCD

Establish Baseline – original PDB files:•  Take PDBs•  Extract ligand coordinates•  Run REFMAC5 to assess geometry (idealisation mode)

Re-refined PDB using AceDRG dictionary (monomer library update)•  Extract ligand coordinates•  Run REFMAC5 to assess geometry (idealisation mode)

Compare with CSD model:•  Take coordinates•  Run REFMAC5 to assess geometry (idealisation mode)

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PDB ligands

REFMAC5 function value

Frequency

010

2030

4050

10 100 1000 10000

PDB ligands

REFMAC5 function value

Frequency

010

2030

4050

10 100 1000 10000

7

PDB ligands

REFMAC5 function value

Frequency

010

2030

4050

10 100 1000 10000

8

PDB ligands

REFMAC5 function value per atom

Frequency

020

4060

80

0.1 1 10 100 1000

9

DifferentnumbersofmoleculesinPDBfile.OnlyeveroneinCCD/CSDfile.Differentnumberofatomsindifferentligands.SoluGon:scalebynumberofatoms.

Mostligands(250/323)presentonce.Somearepresent2-11Gmes.3h6ihas102DMFligands.

PDB ligands

REFMAC5 function value per atom

Frequency

020

4060

80

0.1 1 10 100 1000

10

PDB ligands

REFMAC5 function value per atom

Frequency

020

4060

80

0.1 1 10 100 1000

11

PDB ligands

REFMAC5 function value per atom

Frequency

020

4060

80

0.1 1 10 100 1000

12

ANL : 2ov47 atomsf = 3435

PDB ligands Re-Refined with AceDRG

REFMAC5 function value per atom

Frequency

020

4060

80100

0.1 1 10 100 1000

13

CSD ligands (CCD representatives)

REFMAC5 function value per atom

Frequency

020

4060

80100

0.1 1 10 100 1000

14

-0.5 0.0 0.5 1.0

-10

12

3

QQ-Plot - REFMAC5 function value per atom

PDB ligands Re-Refined with AceDRG

CS

D li

gand

s (C

CD

repr

esen

tativ

es)

15

-0.5 0.0 0.5 1.0

-10

12

3

REFMAC5 function value per atom

PDB ligands Re-Refined with AceDRG

CS

D li

gand

s (C

CD

repr

esen

tativ

es)

16

-0.5 0.0 0.5 1.0

-10

12

3

REFMAC5 function value per atom

PDB ligands Re-Refined with AceDRG

CS

D li

gand

s (C

CD

repr

esen

tativ

es)

17

AOM4OA1AN3C0

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AOM : 1lho

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AOM : 1lho

AOM (CSD)

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AOM : 1lho

AOM (CSD)

21

AOM : 1lho

AOM (CSD)Refined 1cyc

22

4OA: 4q0a

23

4OA: 4q0a

4OA (CSD)

24

4OA: 4q0a

4OA (CSD)

25

4OA: 4q0a

4OA (CSD)Refined 1cyc

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1AN: 1lgw

27

1AN: 1lgw

1AN (CSD)

28

1AN: 1lgw

1AN (CSD)Refined 1cyc

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3C0: 4u16

30

3C0: 4u16

3C0 (CSD)

31

3C0: 4u16

3C0 (CSD)

32

3C0: 4u16

3C0 (CSD)Refined 1cyc

33

SummaryNotes:•  LigandmaybeinaparGcularconformaGonduetoenvironment–notscoringidealconformaGons

•  RidinghydrogensareaddedbyREFMACandusedforscoring.•  MadeadifferenceforafeworiginalPDBentries(3AQin4txs).•  Nodifferenceinre-refinedorCSDligands.

Conclusions:•  ThereareproblemsintheCSDmodels.

•  CouldinvesGgatefurther,andreporttoCSD.•  Noteissuescouldbeinintermediatesteps–CCD,Coot,etc.

•  Nomenclatureinconsistencies–howdowedealwiththis?

•  NothingconcerningidenGfiedthatshouldmakeuseworriedaboutAceDRG.•  Noextremeoutliersa_erre-refinementwithAceDRG.•  ThereareissuesinthemodelsdepositedinthePDB(nosurprise).