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A Mesoscopic Model for Protein-Protein Interactions in Solution

Lund, Mikael LU and Jönsson, Bo LU (2003) In Biophysical Journal 85(5). p.2940-2947
Abstract
Protein self-association may be detrimental in biological systems, but can be utilized in a controlled fashion for protein crystallization. It is hence of considerable interest to understand how factors like solution conditions prevent or promote aggregation. Here we present a computational model describing interactions between protein molecules in solution. The calculations are based on a molecular description capturing the detailed structure of the protein molecule using x-ray or nuclear magnetic resonance structural data. Both electrostatic and van der Waals interactions are included and the salt particles are explicitly treated allowing investigations of systems containing mono-, di-, and trivalent ions. For three different... (More)
Protein self-association may be detrimental in biological systems, but can be utilized in a controlled fashion for protein crystallization. It is hence of considerable interest to understand how factors like solution conditions prevent or promote aggregation. Here we present a computational model describing interactions between protein molecules in solution. The calculations are based on a molecular description capturing the detailed structure of the protein molecule using x-ray or nuclear magnetic resonance structural data. Both electrostatic and van der Waals interactions are included and the salt particles are explicitly treated allowing investigations of systems containing mono-, di-, and trivalent ions. For three different proteins—lysozyme, -chymotrypsinogen, and calbindin D9k—we have investigated under which conditions (salt concentration, ion valency, pH, and/or solvent) the proteins are expected to aggregate via evaluation of the second virial coefficient. Good agreement is found with experimental data where available. Calbindin is investigated in more detail, and it is demonstrated how changes in solvent and/or counterion valency lead to attractive ion-ion correlation effects. For high valency counterions we have found abnormal trends in the second virial coefficient. With trivalent counterions, attraction of two negatively charged protein molecules can be favored because the repulsive term is decreased for entropic reasons due to the low number of particles present. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biophysical Journal
volume
85
issue
5
pages
2940 - 2947
publisher
Cell Press
external identifiers
  • wos:000186190500015
  • pmid:14581196
  • scopus:0242290876
ISSN
1542-0086
language
English
LU publication?
yes
id
ba056350-ee4f-4d1f-9fe2-d7726662c6b4 (old id 128782)
alternative location
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1303572&blobtype=pdf
http://www.biophysj.org/cgi/content/abstract/85/5/2940
date added to LUP
2007-07-17 12:08:02
date last changed
2018-01-07 05:20:34
@article{ba056350-ee4f-4d1f-9fe2-d7726662c6b4,
  abstract     = {Protein self-association may be detrimental in biological systems, but can be utilized in a controlled fashion for protein crystallization. It is hence of considerable interest to understand how factors like solution conditions prevent or promote aggregation. Here we present a computational model describing interactions between protein molecules in solution. The calculations are based on a molecular description capturing the detailed structure of the protein molecule using x-ray or nuclear magnetic resonance structural data. Both electrostatic and van der Waals interactions are included and the salt particles are explicitly treated allowing investigations of systems containing mono-, di-, and trivalent ions. For three different proteins—lysozyme, -chymotrypsinogen, and calbindin D9k—we have investigated under which conditions (salt concentration, ion valency, pH, and/or solvent) the proteins are expected to aggregate via evaluation of the second virial coefficient. Good agreement is found with experimental data where available. Calbindin is investigated in more detail, and it is demonstrated how changes in solvent and/or counterion valency lead to attractive ion-ion correlation effects. For high valency counterions we have found abnormal trends in the second virial coefficient. With trivalent counterions, attraction of two negatively charged protein molecules can be favored because the repulsive term is decreased for entropic reasons due to the low number of particles present.},
  author       = {Lund, Mikael and Jönsson, Bo},
  issn         = {1542-0086},
  language     = {eng},
  number       = {5},
  pages        = {2940--2947},
  publisher    = {Cell Press},
  series       = {Biophysical Journal},
  title        = {A Mesoscopic Model for Protein-Protein Interactions in Solution},
  volume       = {85},
  year         = {2003},
}