Atomistic Details of Chymotrypsin Conformational Changes upon Adsorption on Silica

Nils Hildebrand, Monika Michaelis, Nina Wurzler, Zhuo Li, Jonathan D. Hirst, András Micsonai, József Kardos, Alejandro Gil-Ley, Giovanni Bussi, Susan Köppen, Massimo Delle Piane, Lucio Colombi Ciacchi

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4 Citations (Scopus)


Adsorption of enzymes on solid surfaces may lead to conformational changes that reduce their catalytic conversion activity and are thus detrimental to the efficiency of biotechnology or biosensing applications. This work is a joint theoretical and experimental endeavor in which we identify and quantify the conformational changes that chymotrypsin undergoes when in contact with the surface of amorphous silica nanoparticles. For this purpose, we use circular dichroism spectroscopy, standard molecular dynamics, and advanced-sampling methods. Only the combination of these techniques allowed us to pinpoint a destabilization effect of silica on specific structural motifs of chymotrypsin. They are linked by the possibility of theoretically predicting CD spectra, allowing us to elucidate the source of the experimentally observed spectral changes. We find that chymotrypsin loses part of its helical content upon adsorption, with minor perturbation of its overall tertiary structure, associated with changes in the aromatic interactions. We demonstrate that the C-terminal helical fragment is unfolded as an isolated oligopeptide in pure water, folded as an α-helix as terminus of chymotrypsin in solution, and again partly disordered when the protein is adsorbed on silica. We believe that the joint methodology introduced in this manuscript has a direct general applicability to investigate any biomolecule-inorganic surface system. Methods to theoretically predict circular dichroism spectra from atomistic simulations were compared and improved. The drawbacks of the approaches are discussed; in particular, the limited capability of advanced-sampling MD schemes to explore the conformational phase space of large proteins and the dependency of the predicted ellipticity bands on the choice of calculation parameters.

Original languageEnglish
Pages (from-to)4036-4050
Number of pages15
JournalACS Biomaterials Science and Engineering
Issue number12
Publication statusPublished - Dec 10 2018



  • circular dichroism
  • conformational changes
  • free energy
  • molecular dynamics
  • protein adsorption
  • silica

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

Cite this

Hildebrand, N., Michaelis, M., Wurzler, N., Li, Z., Hirst, J. D., Micsonai, A., Kardos, J., Gil-Ley, A., Bussi, G., Köppen, S., Piane, M. D., & Ciacchi, L. C. (2018). Atomistic Details of Chymotrypsin Conformational Changes upon Adsorption on Silica. ACS Biomaterials Science and Engineering, 4(12), 4036-4050.