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

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pages4278-4284
Number of pages7
JournalJournal of Physical Chemistry Letters
Volume10
Issue number15
Early online date18 Jul 2019
DOIs
Publication statusPublished - 1 Aug 2019

Fingerprint

silk
Silk
Molecular Structure
Fibroins
drugs
Pharmaceutical Preparations
Conformations
Drug interactions
Molecular Conformation
threads
Molecular Dynamics Simulation
Hydrogen Bonding
Coulomb interactions
Static Electricity
Drug delivery
Drug Interactions
Molecular dynamics
Drug Liberation
delivery
Hydrogen bonds

Keywords

  • well-tempered metadynamics
  • molecular dynamics simulation
  • drug binding and release

Cite this

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title = "Unraveling the impact of high-order silk structures on molecular drug binding and release behaviors",
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.",
keywords = "well-tempered metadynamics, molecular dynamics simulation, drug binding and release",
author = "Thidarat Wongpinyochit and Vassileiou, {Antony D.} and Sukriti Gupta and Mushrif, {Samir H.} and Johnston, {Blair F.} and Seib, {F. Philipp}",
year = "2019",
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AU - Wongpinyochit, Thidarat

AU - Vassileiou, Antony D.

AU - Gupta, Sukriti

AU - Mushrif, Samir H.

AU - Johnston, Blair F.

AU - Seib, F. Philipp

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AB - 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.

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