A coarse-grained xDLVO model for colloidal protein–protein interactions

Pusara, Srdjan; Yamin, Peyman; Wenzel, Wolfgang; Krstić, Marjan; Kozłowska, Mariana

doi:10.1039/d1cp01573g

Cited by 12 publications

(24 citation statements)

References 100 publications

(160 reference statements)

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“…Pusara et al . 210 recently developed a coarse-grained xDLVO model to correct for the spherical approximation on the DLVO theory, though the results only show a modest improvement for predicting values as a function of ionic strength on both globular proteins and immunoglobulins. These results are not surprising, as Grünberger et al .…”

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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“…Notably, it is possible to formulate a more generalized version of eqn (1), which is introduced within our manuscript. 26 From a theoretical point of view, the free energy of the saltdependent binding of BLG can be investigated using molecular dynamics (MD) simulations, 27 but sampling of protein-protein configurations in the total PMF, in eqn (1), beyond the BLG dimer from the crystal structure, was not yet reported. According to the DLVO (Derjaguin, Landau, Verwey, and Overbeek) theory, 28 the PMF consists of the electric double-layer forces and vdW interactions.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the calculation of the PPIs beyond the spherical-shaped particles, as commonly used in DLVO, was introduced within a xDLVOcoarse-grained (CG) model. 26 Beyond the DLVO theory and the extended models, W 22 (a) can be estimated using MD and Monte Carlo simulations with both all-atom 32,33 and CG 34 protein representations. The results of these computationally intensive methods have shown that even if the detailed structural and charge characteristics of the protein is properly preserved, other macroscopic features significantly affect the total PMF.…”

Section: Introductionmentioning

confidence: 99%

Determination of specific and non-specific protein–protein interactions for beta-lactoglobulin by analytical ultracentrifugation and membrane osmometry experiments

et al. 2022

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“…This theory has also been used to study bovine serum interaction to different solid surfaces 33 . This theory has also been modified to study protein–protein interaction 34,35 …”

Section: Introductionmentioning

confidence: 99%

“…33 This theory has also been modified to study protein-protein interaction. 34,35 All these studies suggest that the surface energetics approach, utilizing XDLVO theory, has the potential to understand protein interaction to ion exchange chromatographic supports, which has never been attempted earlier. Hence, this study is an attempt to find out the interaction behavior of proteins to ion exchange chromatographic material by XDLVO theory/surface energetics approach.…”

Section: Introductionmentioning

confidence: 99%

Understanding the interaction of proteins to ion exchange chromatographic supports: A surface energetics approach

Aasim

Khan

Bibi

et al. 2022

Biotechnology Progress

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Ion exchange chromatography is one of the most widely used chromatographic technique for the separation and purification of important biological molecules. Due to its wide applicability in separation processes, a targeted approach is required to suggest the effective binding conditions during ion exchange chromatography. A surface energetics approach was used to study the interaction of proteins to different types of ion exchange chromatographic beads. The basic parameters used in this approach are derived from the contact angle, streaming potential, and zeta potential values.The interaction of few model proteins to different anionic and cationic exchanger, with different backbone chemistry, that is, agarose and methacrylate, was performed.Generally, under binding conditions, it was observed that proteins having negative surface charges showed strong to lose interaction (20 kT for Hannilase to 0.5 kT for IgG) with different anionic exchangers (having different positive surface charges). On the contrary, anionic exchangers showed almost no interaction (0-0.1 kT) with the positively charged proteins. An inverse behavior was observed for the interaction of proteins to cationic exchangers. The outcome from these theoretical calculations can predict the binding behavior of different proteins under real ion exchange chromatographic conditions. This will ultimately propose a better bioprocess design for protein separation.

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A coarse-grained xDLVO model for colloidal protein–protein interactions

Abstract: Colloidal protein-protein interactions (PPIs) of attractive and repulsive nature modulate the solubility of proteins, their aggregation, precipitation and crystallization. Such interactions are very important for many biotechnological processes, but are...

Cited by 12 publications

References 100 publications

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

Computational models for studying physical instabilities in high concentration biotherapeutic formulations

Determination of specific and non-specific protein–protein interactions for beta-lactoglobulin by analytical ultracentrifugation and membrane osmometry experiments

Understanding the interaction of proteins to ion exchange chromatographic supports: A surface energetics approach

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