BibTex format
@article{Saurabh:2023:10.1080/00268976.2023.2236248,
author = {Saurabh, S and Li, Z and Hollowell, P and Waigh, T and Li, P and Webster, J and Seddon, JM and Kalonia, C and Lu, JR and Bresme, F},
doi = {10.1080/00268976.2023.2236248},
journal = {Molecular Physics: An International Journal at the Interface Between Chemistry and Physics},
pages = {1--16},
title = {Structure and interaction of therapeutic proteins in solution: a combined simulation and experimental study},
url = {http://dx.doi.org/10.1080/00268976.2023.2236248},
volume = {121},
year = {2023}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The aggregation of therapeutic proteins in solution has attracted significant interest, driving efforts to understand the relationship between microscopic structural changes and protein-protein interactions determining aggregation processes in solution. Additionally, there is substantial interest in being able to predict aggregation based on protein structure as part of molecular developability assessments. Molecular Dynamics provides theoretical tools to complement experimental studies and to interrogate and identify the microscopic mechanisms determining aggregation. Here we perform all-atom MD simulations to study the structure and inter-protein interaction of the Fab and Fc fragments of the monoclonal antibody (mAb) COE3. We unravel the role of ion-protein interactions in building the ionic double layer and determining effective inter-protein interaction. Further, we demonstrate, using various state-of-the-art force fields (charmm, gromos, amber, opls/aa), that the protein solvation, ionic structure and protein-protein interaction depend significantly on the force field parameters. We perform SANS and Static Light Scattering experiments to assess the accuracy of the different forcefields. Comparison of the simulated and experimental results reveal significant differences in the forcefields' performance, particularly in their ability to predict the protein size in solution and inter-protein interactions quantified through the second virial coefficients. In addition, the performance of the forcefields is correlated with the protein hydration structure.
AU - Saurabh,S
AU - Li,Z
AU - Hollowell,P
AU - Waigh,T
AU - Li,P
AU - Webster,J
AU - Seddon,JM
AU - Kalonia,C
AU - Lu,JR
AU - Bresme,F
DO - 10.1080/00268976.2023.2236248
EP - 16
PY - 2023///
SN - 0026-8976
SP - 1
TI - Structure and interaction of therapeutic proteins in solution: a combined simulation and experimental study
T2 - Molecular Physics: An International Journal at the Interface Between Chemistry and Physics
UR - http://dx.doi.org/10.1080/00268976.2023.2236248
VL - 121
ER -