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Welcome ! Mass Spectrometry meets ChemInformatics Tobias Kind and Julie Leary UC Davis Course 3: Mass spectral and molec PowerPoint Presentation
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Mass Spectrometry meets ChemInformatics

Tobias Kind and Julie Leary

UC Davis

Course 3: Mass spectral and moleculardatabase search

Class website: CHE 241 - Spring 2008 - CRN 16583


PPT is hyperlinked – please change to Slide Show Mode


Molecules and mass spectra

Close relationship between molecular structure and mass spectra

Molecular structure is reflected in mass spectral features

(peaks, peak heights and peak combinations)

Mass spectra reflect a state of gas phase ion physics and chemistry

(rearrangements, fragmentations, bond cleavages)

Electron impact (70 eV) mass spectra; Source: NIST05


Molecules and mass spectra

Similar structures may or may have not similar mass spectra

Electron impact (70 eV) mass spectra; Source: NIST05; Created using structure similarity search in NIST MS Search program


Molecules and mass spectra

Similar mass spectra may or may have not similar structures

Electron impact (70 eV) mass spectra; Source: NIST05; Created using spectral similarity search in NIST MS Search program


Mass spectral databases I

Name Spectra count Type

NIST05 200,000 electron impact spectra (EI 70 eV)

Wiley 8 400,000 electron impact spectra (EI 70 eV)

Palisade 600K 600,000 electron impact spectra (EI 70 eV)

NIST MS/MS 5,200 MS/MS (ESI, +/-, 30-100V CID)

MassFrontier 7,000 MSn, ESI,(Spectral Tree Library )

Important is data quality

Annotation with CAS and Structure and Formula

Link to literature or publication useful

Currently no large ESI,APPI,APCI libraries available (free or commercial)


Mass spectral databases II

Smaller specialized libraries

Pfleger Maurer Weber (Drugs) MS+RI, 70eV

MassFinder (Volatiles) MS+RI, 70eV

RIZA DB (Toxicants) MS+RI, 70eV

Golm DB (primary Metabolites) MS+RI, 70eV

Fiehnlib (primary Metabolites) MS+RI, 70eV

MassBank (Metabolites) ESI, MSn ,accurate masses

AAFS (Drugs, Forensic,Toxicology), MS+RI, 70eV

ChemicalSoft (Drugs), MS/MS, MSE


In case of electron impact (EI) same GC-Column (DB-5, RTX-5, DB-1, OV-1)

and temperature program must be used for matching retention indices

In case of ESI, APPI spectra (LC-MS) same mass spectrometer design

and setup should be used (triple-quad, ion-trap, TOF, Q-TOF), collision energy


Mass spectral search algorithms

PBM - Probability Based Matching (McLafferty & Stauffer) – since 1976

Dot Product (Finnigan/INCOS) – since 1978

Weighted Dot Product (Stein) – since 1993

Mass Spectral Tree Search (Mistrik)– since 21st century

WeightedDot Product:

Au and Ar: are the abundances of peaks in the user and reference mass spectra

m: m/z values

w: weighting term

Source: Stein S.E. see notes


NISTMS mass spectral search

The NIST MS Search program is the “gold standard” for EI spectral searchUsed for all types of unit resolution spectra MS/MS, APCI, ESI-MS spectra


NIST MS Search program 2.0

Search everything:

A) Library Search: Reverse, Normal, Similarity, Neutral Loss

B) Structure Similarity Search: find molecules similar to

C) Formula Search: find C11H13N3O3S

D) Constrained peak search: find peaks with m/z 122 and 188 and 266

E) Name search: find Stuntman (maleic hydrazide)

Search Connections:

Import/Export molecular structures: (msp, hpj, sdf)

Interpret Structures (MSInterpreter.exe)

Find substructures (expert algorithm)

Import spectra from other programs (AMDIS, Chemstation, ChromaTOF)

[Download] – freely available (NIST05 MS Library is licensed ~ $1200)


Mass Spectral Trees in Mass Frontier

MassFrontiersearches MSn and CID mass spectra

Source: MassFrontier Helpfile


Mass spectral search

  • Library search is always the first step during the identification process.
  • Usually library search is not enough to assign unique isomer structures.
  • Mass spectra must be clean and background free before search.
  • For LC-MS and GC-MS this requires peak picking and deconvolution.
  • Additional orthogonal information has to be used:
    • restriction of compound space to certain species or material
    • use of isotope pattern information
    • use of retention index if derived from GC-MS data
    • use of retention – logp or logD correlations in case of LC-MS
    • additional fragmentation at different voltages (MSE)

Only certain mass spectra can be in-silico predicted (calculated)

(peptides, lipids, carbohydrates) – this is not the rule for other molecules


MALDI MS based proteomics

Clinical Science Clin. Sci. (2005) 108, 369-383


LC-MS based proteomics approach

Source: Paul Rudnick / NIST


Proteomics data analysis (pipeline)

General approaches A) database search (Sequest, Mascot, OMSSA)

B) de-novo sequencing (Peaks, Lutefisk, Pepnovo)

C) hybrid methods (GutenTag, Popitam, Inspect)

Picture Source: Paul Rudnick / NIST


OMSSA- Open mass spectrometry search algorithm

  • submit spectra to MS/MS search
  • in-silico digestion of proteins
  • matching of experimental vs. calculated MSn
  • hit score computation
  • inspection and review of results

Download OMSSA

Source: OMSSA (NCBI)


Mass spectral search of peptides (new)

See also ProMEX (MPIMP Golm)

Source: Paul Rudnick / NIST


Conversion of mass spectral libraries

Usually a hassle. Keep a copy of libraries always in non-proprietary format.

Request export functions or converters from your mass spec producer.

XCalibur LibraryManager.exe

Thermo Electron Fisher Finnigan MAT ICIS/GCQ/ITS 40 (*.lib, *.lbr)

AutoMass (*.spr, *.prs, *.nam, *.hdr, *.fsf, *.cfs)

MassLab (*.idb) to NIST and vice versa


Spectral files *.msd, *.hpj, *.sdf


JCAMP-DX, (*.jdx *.hpj)


How to search molecules

Exact search

Substructure search

Similarity search

Ligand search

R-group/Markush search


NIST MS DB has structure similarity search

Good for comparing mass spectra of similar compounds (may have similar mass spectra)


Searching Molecules on PubChem

18 million compound DB (++)

Goto PubChem Structure Search


CAS SciFinder

  • 33 million molecules and 60 million peptides/proteins
  • largest reaction DB (14 million reactions) and literature DB
  • substructure and similarity search of structures
  • a must for chemists and biochemists/biologists
  • no bulk download, no good Import/ Export, no Link outs

Download Scifinder


Structure search in SciFinder

Retrieved 4000 papers

(refine search only MS and MALDI)







How scientist publish mass spectra (*)


Scientist A

Runs MS

Publication on paperas bitmap graphic

Scientist B

Needs DB


DB Curation

DB Creation

Sell DB



Central and Open Repository

Electronic Publishing in XML

Computerized Free or Paid Curation

OCR – optical character recognition

DB – database

(*) – and structures and other spectral data


Open data repository for mass spectra

Submit spectra before publication (ticket system)

No loss of information (high resolution spectra)

No truncated data (report five peaks only)

No hamburger to cow algorithm needed (OCR)

Fast and instant use with no restrictions

New synergism for data interpretation

Can still cost money (curation)

Works in genomic sciences (GenBank)

Commercial use may be possible


Central and Open


… checkout the BlueObelisk


The Last Page - What is important to remember

  • There are different search types for mass spectral data
  •  similarity search, reverse search, neutral loss search, MS/MS search
  • There are large libraries for electron impact spectra (EI) from GC-MS
  • There are no large open/commercial libraries for spectra from LC-MS
  • For creation of mass spectral libraries a holistic approach is important
  • Mass spectral trees can give further information (MSE or MSn)
  • There are different types of searching structures
  • Exact search, similarity search, substructure search

Before you start a research project, create target lists of possible candidates

 Collect mass spectra or structures in libraries with references


Reading list (20 min)

Chemical derivatization and mass spectral libraries in metabolic profiling by GC/MS and LC/MS/MS

The critical evaluation of a comprehensive mass spectral library

Development and validation of a spectral library searching method for peptide identification from MS/MS

Additional reading list for very diligent and interested pupils (30 min) (*)

An MS/MS Library on an Ion-Trap Instrument for Efficient Dereplication of Natural Products. Different Fragmentation Patterns for [M + H]+ and [M + Na]+ Ions

The History of the NIST/EPA/NIH Mass Spectral Database


(*) Edison: “Two per cent is genius and 98 per cent is hard work”

“Bah. Genius is not inspired. Inspiration is perspiration” [SOURCE]


Tasks (7 min):

Should be solved and may be graded

  • Goto PubChem [LINK] or Chemspider [LINK] and perform the 3 different
  • structure searches using benzene; report on the number of results
  • (use the sketch function to draw benzene (6 ring with 3 aromatic bonds))
  • 2) Download NIST MS Search [LINK] and perform the 3 different mass spectral searches on cocaine
  • (download JAMP-DX from NIST [link])
  • 3) Use Instant-JChem [LINK] from last course session and create a local demo
  • database with PubChem data.
  • Perform 3 different structure searches with benzene by double-clickingon the structure search field. Report number of results.
  • Additional task for proteomics candidates:
  • 4) Download the NIST peptide search [LINK] and perform a search on the given examples

Link List

High-resolution mass spectral database (fragrances, terpenoid mass spectra SE-52 column + RIs)