title: A physical picture for mechanical dissociation of biological complexes: from forces to free energies.
abstract: Single-molecule force spectroscopy is a powerful technique based on the application of controlled forces to macromolecules. In order to relate the measured response of the molecule to its equilibrium and dynamic properties, a suitable physical picture of the involved process is necessary. In this work, we introduce a plausible model for mechanical unbinding of some molecular complexes, based on a novel free energy profile. We combine two standard theoretical frameworks for analyzing force spectroscopy experiments on two protein:protein complexes, obtaining key magnitudes of the underlying free energy profile, which are only understood within the mentioned model. Additionally, we carry out detailed stochastic dynamics simulations to prove the validity of the analysis protocol and the reliability of the free energy profile. Remarkably, we can compare directly the obtained unbinding free energies with the previously known bulk binding free energies, bridging the gap between bulk and single molecule techniques.
authors.affiliation: Instituto de Biocomputación y Física de Sistemas Complejos and Departamento de Física de la Materia Condensada, Universidad de Zaragoza, 50009 Zaragoza, Spain. fff@unizar.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Tapia-Rojo
authors.affiliation: Laboratorio de Microscopías Avanzadas, Instituto de Nanociencia de Aragón, Universidad de Zaragoza, 50018 Zaragoza, Spain and Fundación INA, 50018 Zaragoza, Spain.
authors.forename: Carlos
authors.identifier: http://orcid.org/0000-0003-3459-8605
authors.initials: C
authors.lastname: Marcuello
authors.affiliation: Laboratorio de Microscopías Avanzadas, Instituto de Nanociencia de Aragón, Universidad de Zaragoza, 50018 Zaragoza, Spain and Fundación INA, 50018 Zaragoza, Spain and Fundación ARAID, 50018 Zaragoza, Spain.
authors.forename: Anabel
authors.identifier: http://orcid.org/0000-0001-7460-5916
authors.initials: A
authors.lastname: Lostao
authors.affiliation: Laboratorio de Microscopías Avanzadas, Instituto de Nanociencia de Aragón, Universidad de Zaragoza, 50018 Zaragoza, Spain and Fundación INA, 50018 Zaragoza, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gómez-Moreno
authors.affiliation: Instituto de Ciencia de Materiales de Aragón and Departamento de Física de la Materia Condensada, Universidad de Zaragoza, 50009 Zaragoza, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: J Mazo
authors.affiliation: Instituto de Biocomputación y Física de Sistemas Complejos and Departamento de Física de la Materia Condensada, Universidad de Zaragoza, 50009 Zaragoza, Spain. fff@unizar.es.
authors.forename: Fernando
authors.identifier: http://orcid.org/0000-0002-9551-624X
authors.initials: F
authors.lastname: Falo
mesh_terms: D019277:Entropy; D007700:Kinetics; D008956:Models, Chemical; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D013057:Spectrum Analysis; D013816:Thermodynamics
chemical_list: D046912:Multiprotein Complexes