PMID- 27225419
OWN - NLM
STAT- MEDLINE
DCOM- 20180914
LR  - 20181202
IS  - 1879-1123 (Electronic)
IS  - 1044-0305 (Print)
IS  - 1044-0305 (Linking)
VI  - 27
IP  - 9
DP  - 2016 Sep
TI  - Optimization of Electrospray Ionization by Statistical Design of Experiments and 
      Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant 
      Determinations.
PG  - 1520-30
LID - 10.1007/s13361-016-1417-x [doi]
AB  - Electrospray ionization mass spectrometry (ESI-MS) binding studies between 
      proteins and ligands under native conditions require that instrumental ESI source 
      conditions are optimized if relative solution-phase equilibrium concentrations 
      between the protein-ligand complex and free protein are to be retained. 
      Instrumental ESI source conditions that simultaneously maximize the relative 
      ionization efficiency of the protein-ligand complex over free protein and 
      minimize the protein-ligand complex dissociation during the ESI process and the 
      transfer from atmospheric pressure to vacuum are generally specific for each 
      protein-ligand system and should be established when an accurate equilibrium 
      dissociation constant (KD) is to be determined via titration. In this paper, a 
      straightforward and systematic approach for ESI source optimization is presented. 
      The method uses statistical design of experiments (DOE) in conjunction with 
      response surface methodology (RSM) and is demonstrated for the complexes between 
      Plasmodium vivax guanylate kinase (PvGK) and two ligands: 5'-guanosine 
      monophosphate (GMP) and 5'-guanosine diphosphate (GDP). It was verified that even 
      though the ligands are structurally similar, the most appropriate ESI conditions 
      for KD determination by titration are different for each. Graphical Abstract ᅟ.
FAU - Pedro, Liliana
AU  - Pedro L
AD  - Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, 
      Australia.
FAU - Van Voorhis, Wesley C
AU  - Van Voorhis WC
AD  - Department of Medicine, University of Washington, Seattle, WA, USA.
FAU - Quinn, Ronald J
AU  - Quinn RJ
AD  - Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, 
      Australia. r.quinn@griffith.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160525
PL  - United States
TA  - J Am Soc Mass Spectrom
JT  - Journal of the American Society for Mass Spectrometry
JID - 9010412
RN  - 0 (Ligands)
RN  - 0 (Proteins)
SB  - IM
MH  - Ligands
MH  - Proteins/*chemistry
MH  - Spectrometry, Mass, Electrospray Ionization
PMC - PMC4972871
OTO - NOTNLM
OT  - ESI-FTMS
OT  - Kd
OT  - Plasmodium vivax Guanylate Kinase (PvGK)
OT  - Protein-ligand complex
EDAT- 2016/05/27 06:00
MHDA- 2018/09/15 06:00
PMCR- 2016/05/25
CRDT- 2016/05/27 06:00
PHST- 2014/11/02 00:00 [received]
PHST- 2016/05/04 00:00 [accepted]
PHST- 2016/04/29 00:00 [revised]
PHST- 2016/05/27 06:00 [entrez]
PHST- 2016/05/27 06:00 [pubmed]
PHST- 2018/09/15 06:00 [medline]
PHST- 2016/05/25 00:00 [pmc-release]
AID - 10.1007/s13361-016-1417-x [pii]
AID - 1417 [pii]
AID - 10.1007/s13361-016-1417-x [doi]
PST - ppublish
SO  - J Am Soc Mass Spectrom. 2016 Sep;27(9):1520-30. doi: 10.1007/s13361-016-1417-x. 
      Epub 2016 May 25.