Rigorous analysis of static light scattering measurements on buffered protein solutions

Wills, Peter R.; Winzor, Donald J.

doi:10.1016/j.bpc.2017.07.007

Cited by 10 publications

(8 citation statements)

References 36 publications

(81 reference statements)

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“… 220 , 221 However, due to the inherent assumptions regarding protein morphology and the nature of the intermolecular interactions, this model might lead to overestimation of net protein interactions and cluster formation when the solution behavior is dominated by strong protein-protein/excipient interactions. 201 , 221 , 222 …”

Section: Protein-protein and Protein-excipient Interactionsmentioning

confidence: 99%

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

Blanco

2022

mAbs

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Computational prediction of the behavior of concentrated protein solutions is particularly advantageous in early development stages of biotherapeutics when material availability is limited and a large set of formulation conditions needs to be explored. This review provides an overview of the different computational paradigms that have been successfully used in modeling undesirable physical behaviors of protein solutions with a particular emphasis on high-concentration drug formulations. This includes models ranging from all-atom simulations, coarse-grained representations to macro-scale mathematical descriptions used to study physical instability phenomena of protein solutions such as aggregation, elevated viscosity, and phase separation. These models are compared and summarized in the context of the physical processes and their underlying assumptions and limitations. A detailed analysis is also given for identifying protein interaction processes that are explicitly or implicitly considered in the different modeling approaches and particularly their relations to various formulation parameters. Lastly, many of the shortcomings of existing computational models are discussed, providing perspectives and possible directions toward an efficient computational framework for designing effective protein formulations.

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Section: Protein-protein and Protein-excipient Interactionsmentioning

confidence: 99%

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

Blanco

2022

mAbs

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“…Even though, a direct conversion of 22 to 22 [35] involves the partial molar volume of the particle which may not be available in the literature, we can exploit an equivalent form of the stability condition, Eq. (15b), which comes from the monotonous relationship between and 2 [41]. Hence, both molarity-and molality-based virial coefficients can be used as the measure of stability.…”

Section: Evidence From Osmotic Stability Via Ultracentrifugation and Scatteringmentioning

confidence: 99%

Thermodynamic stability condition can judge whether a nanoparticle dispersion can be considered a solution in a single phase

Shimizu

Matubayasi

2020

Journal of Colloid and Interface Science

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“…8 Scattering experiments, such as static light scattering and small-angle x-ray scattering (SAXS) experiments, can provide approximate estimates for B ij . 13,14 K d and B ij are crucial quantities to relate molecular simulations of interacting proteins to experiment. Such comparisons become increasingly important as molecular simulations of crowded cell-like environments have become computationally feasible, even in full atomic detail.…”

Section: Introductionmentioning

confidence: 99%

Quantifying Protein-Protein Interactions in Molecular Simulations

Quoika¹,

Linke²,

Hummer³

et al. 2019

Preprint

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<a></a><a></a>We present simple, accurate, and efficient methods to estimate the dissociation constant Kd and the second osmotic virial coefficient B2 from molecular simulations. We show that for simulations of two proteins in a box, Kd is determined by B2 and the fraction of bound protein. We present two different methods to calculate B2 from Monte Carlo and molecular dynamics simulations using implicit or explicit solvent. We derive a surprisingly simple expression for B2, adding significantly to the understanding of this important quantity. Non-binding interactions of proteins and other macromolecules shape the physicochemical properties of the crowded environments inside cells and of biomolecular condensates. We show how to extract the contributions of non-binding conformations to B2 and discuss how these can be determined in analytical ultracentrifugation and SAXS experiments. We expect that our methods will prove to be instrumental in force parameterization efforts and high-throughput studies of large interactomes.

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Rigorous analysis of static light scattering measurements on buffered protein solutions

Cited by 10 publications

References 36 publications

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

Thermodynamic stability condition can judge whether a nanoparticle dispersion can be considered a solution in a single phase

Quantifying Protein-Protein Interactions in Molecular Simulations

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