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Int. J. Mol. Sci. 2016, 17(6), 853; doi:10.3390/ijms17060853

Identification of Protein–Excipient Interaction Hotspots Using Computational Approaches

1
EPSRC Centre for Innovative Manufacturing in Emergent Macromolecular Therapies, University College London, Biochemical Engineering Department, Bernard Katz Building, Gordon Street, London WC1H 0AH, UK
2
UCL School of Pharmacy, Department of Pharmaceutics, 29-39 Brunswick Square, London WC1N 1AX, UK
3
Department of Pharmacy, Pharmacology and Postgraduate Medicine, University of Hertfordshire, College Lane, Hatfield AL10 9AB, UK
*
Authors to whom correspondence should be addressed.
Academic Editor: Tatyana Karabencheva-Christova
Received: 18 February 2016 / Revised: 12 April 2016 / Accepted: 24 May 2016 / Published: 1 June 2016
(This article belongs to the Collection Proteins and Protein-Ligand Interactions)
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Abstract

Protein formulation development relies on the selection of excipients that inhibit protein–protein interactions preventing aggregation. Empirical strategies involve screening many excipient and buffer combinations using force degradation studies. Such methods do not readily provide information on intermolecular interactions responsible for the protective effects of excipients. This study describes a molecular docking approach to screen and rank interactions allowing for the identification of protein–excipient hotspots to aid in the selection of excipients to be experimentally screened. Previously published work with Drosophila Su(dx) was used to develop and validate the computational methodology, which was then used to determine the formulation hotspots for Fab A33. Commonly used excipients were examined and compared to the regions in Fab A33 prone to protein–protein interactions that could lead to aggregation. This approach could provide information on a molecular level about the protective interactions of excipients in protein formulations to aid the more rational development of future formulations. View Full-Text
Keywords: molecular docking; protein–excipient interactions; protein stability; molecular dynamics; Fab formulation molecular docking; protein–excipient interactions; protein stability; molecular dynamics; Fab formulation
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MDPI and ACS Style

Barata, T.S.; Zhang, C.; Dalby, P.A.; Brocchini, S.; Zloh, M. Identification of Protein–Excipient Interaction Hotspots Using Computational Approaches. Int. J. Mol. Sci. 2016, 17, 853.

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