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Atomistic details of chymotrypsin conformational changes upon adsorption on silica

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


Nils Hildebrand

Monika Michaelis

Nina Wurzler

Zhuo Li

András Micsonai

József Kardos

Alejandro Gil-Ley

Giovanni Bussi

Susan Köppen

Massimo Delle Piane

Lucio Colombi Ciacchi


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 to 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.

Keywords: Protein adsorption, Silica, Circular dichroism, Molecular dynamics, Free energy, Conformational changes


Hildebrand, N., Michaelis, M., Wurzler, N., Li, Z., Hirst, J. D., Micsonai, A., …Ciacchi, L. C. (2018). Atomistic details of chymotrypsin conformational changes upon adsorption on silica. ACS Biomaterials Science and Engineering, doi:10.1021/acsbiomaterials.8b00819

Journal Article Type Article
Acceptance Date Oct 25, 2018
Online Publication Date Nov 6, 2018
Publication Date Nov 6, 2018
Deposit Date Nov 16, 2018
Publicly Available Date Nov 7, 2019
Journal ACS Biomaterials Science & Engineering
Electronic ISSN 2373-9878
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Public URL
Publisher URL


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