@article{1f2b3fd8e0824949a53581c8c1c07294,
title = "Development of a Fast Screening Method for Selecting Excipients in Formulations using MD simulations, NMR and MicroScale Thermophoresis",
abstract = "Development of peptide therapeutics generally involves screening of excipients that inhibit peptide-peptide interactions, hence aggregation, and improve peptide stability. We used the therapeutic peptide plectasin to develop a fast screening method that combines microscale thermophoresis titration assays and molecular dynamics simulations to relatively rank the excipients with respect to binding affinity and to study key peptide-excipient interaction hotspots on a molecular level, respectively. Additionally, 1H-13C-HSQC NMR titration experiments were performed to validate the fast screening approach. The NMR results are in qualitative agreement with results from the fast screening method demonstrating that this approach can be reliably applied to other peptides and proteins as a fast screening method to relatively rank excipients and predict possible excipient binding sites.",
keywords = "Chemical shift perturbations, Excipients, FTMap, Hotspots, Microscale thermophoresis, Molecular dynamics simulations, NMR",
author = "Sowmya Indrakumar and Matja Zalar and Nuska Tschammer and Christin Pohl and Allan N{\o}rgaard and Werner Streicher and Pernille Harris and Golovanov, {Alexander P} and {H J Peters}, G{\"u}nther",
note = "Funding Information: This study was funded by a project part of the EU Horizon 2020 Research and Innovation program under the Marie Sk{\l}odowska-Curie grant agreement No 675074 – “Protein-excipient Interactions and Protein-Protein Interactions in formulation” (PIPPI); www.pippi.kemi.dtu.dk. Simulations were performed on the CPU/GPU cluster at DTU Chemistry and the High Performance Computing cluster at DTU. NMR experiments were performed in the NMR Facility at the Manchester Institute of Biotechnology, The University of Manchester. MST experiments were performed at Nanotemper GmbH, Munich. Viscosities were measured at Ludwig Maximilian University of Munich, Germany with help from Dr. Hristo Svilenov and Dr. Andreas Tosstorff from the group of Professor Gerhard Winter. Publisher Copyright: {\textcopyright} 2020 Elsevier B.V. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2021",
month = jan,
day = "1",
doi = "10.1016/j.ejpb.2020.10.015",
language = "English",
volume = "158",
pages = "11--20",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier BV",
}