Atomistic Details of Chymotrypsin Conformational Changes upon Adsorption on Silica
| Autor: | Nina Wurzler, Zhuo Li, Lucio Colombi Ciacchi, András Micsonai, Monika Michaelis, Alejandro Gil-Ley, Susan Köppen, Giovanni Bussi, Nils Hildebrand, Jonathan D. Hirst, Massimo Delle Piane, József Kardos |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Circular dichroism
Biomedical Engineering Nanoparticle 02 engineering and technology 010402 general chemistry 01 natural sciences Settore FIS/03 - Fisica della Materia Biomaterials Molecular dynamics Adsorption conformational changes Structural motif Chymotrypsin biology Chemistry 021001 nanoscience & nanotechnology free energy protein adsorption Protein tertiary structure molecular dynamics 0104 chemical sciences circular dichroism Chemical physics silica biology.protein sense organs 0210 nano-technology Protein adsorption |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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