Force-Dependent Folding and Unfolding Kinetics in DNA Hairpins Reveals Transition-State Displacements along a Single Pathway

Biomolecules diffusively explore their energy landscape overcoming energy barriers via thermally activated processes to reach the biologically relevant conformation. Mechanically induced unfolding and folding reactions offer an excellent playground to feature these processes at the single-molecule l...

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Detalhes bibliográficos
Autores: Alemany, Anna, Ritort Farran, Fèlix, Rico Pastó, Marc
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2017
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/214309
Acesso em linha:https://hdl.handle.net/2445/214309
Access Level:Acceso aberto
Palavra-chave:Genètica
Molècules
Energia
Genetics
Molecules
Energy
Descrição
Resumo:Biomolecules diffusively explore their energy landscape overcoming energy barriers via thermally activated processes to reach the biologically relevant conformation. Mechanically induced unfolding and folding reactions offer an excellent playground to feature these processes at the single-molecule level by monitoring changes in the molecular extension. Here we investigate two-state DNA hairpins designed to have the transition states at different locations. We use optical 8 tweezers to characterize the force-dependent behavior of the kinetic barrier from nonequilibrium pulling experiments by using the continuous effective barrier approach (CEBA). We introduce the mechanical fragility and the molecular transition-state susceptibility, both useful quantities to characterize the response of the transition state to an applied force. Our results demonstrate the validity of the Leffler Hammond postulate where the transition state approaches the folded state as force increases, implying monotonically decreasing fragility with force and a non negative transition state susceptibility at all forces.