X-ray Validation PackagePresent status

Swanand GorePDBe

D&A meeting : 21-Oct-2010

VTF recommendations• Model-based indicators

– Covalent geometry (E&H) outliers– Protein backbone (Ramachandran) and sidechains (rotamericity,

flips) outliers– RNA backbone (atypical suites)– Carbohydrates chirality and naming– Ligands

• Features not observed in high-quality small-molecule xtal structures and other instances in PDB

– Packing• Bad vdw clashes• Underpacking, voids• Unusual contacts• Unsatisfied hbond donors, acceptors

VTF recommendations• Data-based indicators

– Wilson plot– Data anisotropy plot– Twinning (Padilla Yeates plot)– Mislabelling of amplitudes / intensities– Translational NCS– Missed symmetry

• Data and model based indicators– R, Rfree

• Reproducibility and difference– Real-space R

• Per-residue measure of fit with 2FoFc map, normalized per residue type

VTF recommendations

• Percentile scores– Per criterion, calculate

the percentile rank against the whole set of X-ray entries and also against structures in its resolution bin

– Update the percentiles periodically

VTF recommendations

• Presentation of results for various consumers– Depositors (and annotators)– Reviewers• Concise PDF report highlighting any unusual features

– End-users (experts and non-experts)• Web-based frontends with adjustable level of detail

– Developers• Webservices and XML files

VTF recommendations

• Validation package– Be open-source and freely distributable• wwPDB sites, labs, companies

– Import/wrap existing 3rd party functionality• EDS (Uppsala), Molprobity, CCDC Mogul, WhatIf• Phenix, CCP4• RosettaHoles, pdb-care, DACA, ProSA

– Calculate recommended validation metrics and publish XML file per entry

– Present XML contents in various kinds of reports

Prototypes – Validation Viewer

Entry viewer

Residue and maps viewer

Raw data and plots of

phi-psi, omega, chi,

B-factor, occupancy, RSR, RSCC

New ligand-validation functionality• Mogul is a chemical mining engine developed by CCDC for

small-molecule xtal structures in CSD– Splits query molecule into bond, angle, torsion and ring

substructures– Finds comparable substructures from high-quality small-mol

structures in CSD

• Compares query substructures against CSD distributions– Bonds, angles: Z scores can be computed– Torsions: Z-score is undefined but gives an idea where a torsion

lies w.r.t. distribution– Rings: computes query ring’s torsion RMSD against each

comparable CSD ring, finds mean, stdev of tRMSDs to estimate a Z score for ring

Prototypes – Mogul webservice

Distribution for the

angle from Mogul

2D & 3D views of ligand

Bonds, angles, torsions, rings

with comparable

CSD fragments

Upload or select a ligand

Validation package(installed on each site)

mmCIFunder

depositionD&AAPI

ValidationXML file

(Data, Percentiles)

DistributionsCalculator(Runs yearly)

DistributionsOracle Database(Time-stamped by year)

DistributionsWebservice

(if DB only at PDBe)

D&AWebservers

D&Aclients

ReleasedValidationXML file

D&A pipeline on all sites

wwPDB sites (PDBe - ?)

Public Access

Validation XML

Example annotations• Atom-level

– clashes• Residue-level

– Average B factor, occupancy– Phi-psi, Rama outliers– Sidechain flips, rotamer outliers– RNA backbone and pucker values

• Atom-group-level– Covalent bond-length and angles outliers

• Chain-level– WhatIf Rama score, average RSR, NCS deviation

• Entry-level– Rfree, Clash-score– twinning, tNCS, anisotropy, fit to ideal Wilson plot

Summary• VTF recommendations will be implemented in a

validation package.

• The package will consist of modules which import/wrap 3rd party functionality .

• The package will be open-source and freely distributable.

• A process for periodically updating distributions and validation XMLs will be implemented.