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Structure based descriptors for the estimation of colloidal interactions and protein aggregation propensities.

ABSTRACT: The control of protein aggregation is an important requirement in the development of bio-pharmaceutical formulations. Here a simple protein model is proposed that was used in molecular dynamics simulations to obtain a quantitative assessment of the relative contributions of proteins' net-charges, dipole-moments, and the size of hydrophobic or charged surface patches to their colloidal interactions. The results demonstrate that the strength of these interactions correlate with net-charge and dipole moment. Variation of both these descriptors within ranges typical for globular proteins have a comparable effect. By comparison no clear trends can be observed upon varying the size of hydrophobic or charged patches while keeping the other parameters constant. The results are discussed in the context of experimental literature data on protein aggregation. They provide a clear guide line for the development of improved algorithms for the prediction of aggregation propensities.

SUBMITTER: Brunsteiner M

PROVIDER: S-EPMC3614552 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Structure based descriptors for the estimation of colloidal interactions and protein aggregation propensities.

Brunsteiner Michael M Flock Michaela M Nidetzky Bernd B

PloS one 20130402 4

The control of protein aggregation is an important requirement in the development of bio-pharmaceutical formulations. Here a simple protein model is proposed that was used in molecular dynamics simulations to obtain a quantitative assessment of the relative contributions of proteins' net-charges, dipole-moments, and the size of hydrophobic or charged surface patches to their colloidal interactions. The results demonstrate that the strength of these interactions correlate with net-charge and dipo ...[more]

PMID: 23565169

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Dataset Information

Structure based descriptors for the estimation of colloidal interactions and protein aggregation propensities.

Publications

Structure based descriptors for the estimation of colloidal interactions and protein aggregation propensities.

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