Abstract
A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation.
| Original language | English |
|---|---|
| Pages (from-to) | 921-930 |
| Number of pages | 10 |
| Journal | Journal of Physical Chemistry B |
| Volume | 118 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 30 Jan 2014 |
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ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Materials Chemistry
- Surfaces, Coatings and Films
Cite this
Electrostatic unfolding and interactions of albumin driven by pH changes : A molecular dynamics study. / Baler, K.; Martin, O. A.; Carignano, Marcelo; Ameer, G. A.; Vila, J. A.; Szleifer, I.
In: Journal of Physical Chemistry B, Vol. 118, No. 4, 30.01.2014, p. 921-930.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Electrostatic unfolding and interactions of albumin driven by pH changes
T2 - A molecular dynamics study
AU - Baler, K.
AU - Martin, O. A.
AU - Carignano, Marcelo
AU - Ameer, G. A.
AU - Vila, J. A.
AU - Szleifer, I.
PY - 2014/1/30
Y1 - 2014/1/30
N2 - A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation.
AB - A better understanding of protein aggregation is bound to translate into critical advances in several areas, including the treatment of misfolded protein disorders and the development of self-assembling biomaterials for novel commercial applications. Because of its ubiquity and clinical potential, albumin is one of the best-characterized models in protein aggregation research; but its properties in different conditions are not completely understood. Here, we carried out all-atom molecular dynamics simulations of albumin to understand how electrostatics can affect the conformation of a single albumin molecule just prior to self-assembly. We then analyzed the tertiary structure and solvent accessible surface area of albumin after electrostatically triggered partial denaturation. The data obtained from these single protein simulations allowed us to investigate the effect of electrostatic interactions between two proteins. The results of these simulations suggested that hydrophobic attractions and counterion binding may be strong enough to effectively overcome the electrostatic repulsions between the highly charged monomers. This work contributes to our general understanding of protein aggregation mechanisms, the importance of explicit consideration of free ions in protein solutions, provides critical new insights about the equilibrium conformation of albumin in its partially denatured state at low pH, and may spur significant progress in our efforts to develop biocompatible protein hydrogels driven by electrostatic partial denaturation.
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UR - http://www.scopus.com/inward/citedby.url?scp=84893442580&partnerID=8YFLogxK
U2 - 10.1021/jp409936v
DO - 10.1021/jp409936v
M3 - Article
C2 - 24393011
AN - SCOPUS:84893442580
VL - 118
SP - 921
EP - 930
JO - Journal of Physical Chemistry B Materials
JF - Journal of Physical Chemistry B Materials
SN - 1520-6106
IS - 4
ER -