Unraveling the impact of high-order silk structures on molecular drug binding and release behaviors

Wongpinyochit, Thidarat and Vassileiou, Antony D. and Gupta, Sukriti and Mushrif, Samir H. and Johnston, Blair F. and Seib, F. Philipp (2019) Unraveling the impact of high-order silk structures on molecular drug binding and release behaviors. Journal of Physical Chemistry Letters, 10 (15). pp. 4278-4284. ISSN 1948-7185 (https://doi.org/10.1021/acs.jpclett.9b01591)

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Abstract

Silk continues to amaze: over the past decade, new research threads have emerged that include the use of silk fibroin for advanced pharmaceutics, including its suitability for drug delivery. Despite this ongoing interest, the details of silk fibroin structures and their subsequent drug interactions at the molecular level remain elusive, primarily because of the difficulties encountered in modeling the silk fibroin molecule. Here, we generated an atomistic silk model containing amorphous and crystalline regions. We then exploited advanced well-tempered metadynamics simulations to generate molecular conformations that we subsequently exposed to classical molecular dynamics simulations to monitor both drug binding and release. Overall, this study demonstrated the importance of the silk fibroin primary sequence, electrostatic interactions, hydrogen bonding, and higher order conformation in the processes of drug binding and release.

ORCID iDs

Wongpinyochit, Thidarat ORCID logoORCID: https://orcid.org/0000-0003-1339-6908, Vassileiou, Antony D. ORCID logoORCID: https://orcid.org/0000-0001-8146-8972, Gupta, Sukriti, Mushrif, Samir H., Johnston, Blair F. ORCID logoORCID: https://orcid.org/0000-0001-9785-6822 and Seib, F. Philipp ORCID logoORCID: https://orcid.org/0000-0002-1955-1975;
CORE (COnnecting REpositories)