arXiv subjects

Nicholas Skar-Gislinge

Publications and source records attributed to Nicholas Skar-Gislinge.

4 recordsLinked to original sources

arXiv2026

Beyond uniform screening: electrostatic heterogeneity dictates solution structure of complex macromolecules

The complexity of biomolecular interactions necessitates advanced methodologies to accurately capture their behavior in solution. In this work, we focus on monoclonal antibodies and adopt a multi-scale coarse-graining strategy for their modeling, with particular emphasis on the role of electrostatic interactions. Using scattering experiments, theoretical analysis, and large-scale computer simulations, we explicitly compare two selected case studies-markedly different in their charge distributions. Through mutually corroborating lines of evidence, we demonstrate that conventional approaches relying on electrostatic screening and implicit charge representations fail to capture the structural and thermodynamic properties of antibody solutions when strong charge heterogeneity is present, even at a moderate (amino acid) level of coarse-graining. These findings highlight the importance of a correct treatment of electrostatic interactions and ion screening for heterogeneously- and oppositely-charged colloidal and protein systems. Such considerations are essential to move beyond descriptive models towards a truly predictive framework, with direct implications for the formulation of therapeutics and the treatment of other complex soft-matter systems.

cond-mat.soft↗

arXiv2024

GARCH-Informed Neural Networks for Volatility Prediction in Financial Markets

Volatility, which indicates the dispersion of returns, is a crucial measure of risk and is hence used extensively for pricing and discriminating between different financial investments. As a result, accurate volatility prediction receives extensive attention. The Generalized Autoregressive Conditional Heteroscedasticity (GARCH) model and its succeeding variants are well established models for stock volatility forecasting. More recently, deep learning models have gained popularity in volatility prediction as they demonstrated promising accuracy in certain time series prediction tasks. Inspired by Physics-Informed Neural Networks (PINN), we constructed a new, hybrid Deep Learning model that combines the strengths of GARCH with the flexibility of a Long Short-Term Memory (LSTM) Deep Neural Network (DNN), thus capturing and forecasting market volatility more accurately than either class of models are capable of on their own. We refer to this novel model as a GARCH-Informed Neural Network (GINN). When compared to other time series models, GINN showed superior out-of-sample prediction performance in terms of the Coefficient of Determination ($R^2$), Mean Squared Error (MSE), and Mean Absolute Error (MAE).

q-fin.CP↗

arXiv2023

Using cluster theory to calculate the experimental structure factors of antibody solutions

Monoclonal antibody solutions are set to become a major therapeutic tool in the years to come, capable of targeting various diseases by clever designing their antigen binding site. However, the formulation of stable solutions suitable for patient self-administration typically presents challenges, as a result of the increase in viscosity that often occurs at high concentrations. Here, we establish a link between the microscopic molecular details and the resulting properties of an antibody solution through the characterization of clusters, which arise in the presence of self-associating antibodies. In particular, we find that experimental small-angle X-ray scattering data can be interpreted by means of analytical models previously exploited for the study of polymeric and colloidal objects, based on the presence of such clusters. The latter are determined by theoretical calculations and supported by computer simulations of a coarse-grained minimal model, in which antibodies are treated as Y-shaped colloidal molecules and attractive domains are designed as patches. Using the theoretically-predicted cluster size distributions, we are able to describe the experimental structure factors over a wide range of concentration and salt conditions. We thus provide microscopic evidence for the well-established fact that the concentration-dependent increase in viscosity is originated by the presence of clusters. Our findings bring new insights on the self-assembly of monoclonal antibodies, which can be exploited for guiding the formulation of stable and effective antibody solutions.

cond-mat.soft↗

arXiv2018

A colloid approach to self-assembling antibodies

Concentrated solutions of monoclonal antibodies have attracted considerable attention due to their importance in pharmaceutical formulations, yet their tendency to aggregate and the resulting high solution viscosity has posed considerable problems. It remains a very difficult task to understand and predict the phase behavior and stability of such solutions. Here we present a systematic study of the concentration dependence of the structural and dynamic properties of monoclonal antibodies using a combination of different scattering methods and microrheological experiments. To interpret these data, we use a colloid-inspired approach based on a simple patchy model, which explicitly takes into account the anisotropic shape and the charge distribution of the molecules. Combining theory, simulations and experiments, we are able to disentangle self-assembly and intermolecular interactions and to quantitatively describe the concentration dependence of structural and dynamic quantities such as the osmotic compressibility, the collective diffusion coefficient and the zero shear viscosity over the entire range of investigated concentrations. This simple patchy model not only allows us to consistently describe the thermodynamic and dynamic behavior of mAb solutions, but also provides a robust estimate of the attraction between their binding sites. It will thus be an ideal starting point for future work on antibody formulations, as it provides a quantitative assessment of the effects of additional excipients or chemical modifications on antibody interactions, and a prediction of their effect on solution viscosity.

cond-mat.soft↗