Conformational-functional behaviour of proteins



Víctor Muñoz

Group Leader



Research summary

Our group investigates the conformational – functional behavior of proteins to answer questions concerning the intimate behavior of proteins.



Sborgi L, Verma A, Sadqi M, de Alba E, Muñoz V. Protein folding at atomic resolution: analysis of autonomously folding supersecondary structure motifs by nuclear magnetic resonance. Methods Mol Biol 2013; 932:205-218

Campos LA, Sadqi M, Liu J, Wang X, English DS, Muñoz V. Gradual disordering of the native state on a slow two-state folding protein monitored by single-molecule fluorescence spectroscopy and NMR. J Phys Chem B 2014; 117:13120-13131

Cerminara M, Campos LA, Ramanthan R, Muñoz V. Slow proton transfer coupled to unfolding explain the puzzling results of single-molecule experiments on BBL, a paradigmatic downhill folding protein. PloS ONE 2014; 8:e78044

Sanchez-Medina C, Sekhar A, Vallurupalli P, Cerminara M, Muñoz V, Kay LE. Probing the free energy landscape of the fast-folding gpW protein by relaxation dispersión NMR. J Am Chem Soc 2014; 136:7444-7451

Naganathan AN, Muñoz V. Thermodynamics of downhill folding: multi-probe analysis of PDD, a protein that folds over a marginal free energy barrier. J Phys Chem B 2014; 118:8982-8994


Imagen2MuñozOur group studies the conformational and functional behaviour of proteins using a multidisciplinary approach that combines physical chemistry, advanced molecular spectroscopy (ultrafast and single-molecule), structural biology, computer science, protein engineering, and molecular biology. Our efforts in the last two years have centered on three major areas -- experimental and theoretical analysis of protein folding ensembles, investigation of the molecular rheostat hypothesis, and engineering of macromolecular assemblies.

In reference to analysis of protein folding ensembles, we continued our efforts from previous years in developing a catalogue of folding archetypes corresponding to small single-domain proteins with elementary combinations of secondary structure elements.

Our second area of interest emerged from the experimental discovery of downhill folding, which led us to hypothesise that downhill folding modules can exploit their special behaviour, by which they change structure gradually rather than cooperatively, to implement molecular rheostats. Molecular rheostats are proteins able to produce analogue signals at the single-molecule level rather than the binary outputs of conventional molecular switches. These rheostats could offer a new variety of functional and regulatory properties for processes that depend on quantitative signals at the nanoscale; such devices might be used in nature. They also offer tremendous potential for nanobiotechnological applications. In this area, we recently showed proof of concept of a rheostatic biosensor based on the downhill folding module BBL. In parallel, we analyse the biological roles of conformational rheostats in coordinating protein networks via conformational selection, in the phenomenon of DNA sliding and homing-to-target by transcription factors during gene expression, and as molecular springs in macromolecular assemblies.

In a third research area, we recently embarked on a new project that involves engineering of macromolecular devices from monomeric globular proteins. This effort borrows ideas from molecular evolution to implement a design strategy that would facilitate domain swapping between otherwise monomeric proteins by engineering their folding behaviour in ways that reduce their intrinsic folding cooperativity.





Víctor Muñoz Principal investigator
Eva de Alba Bastarrechea Senior scientist
Mourad Sadqi Senior scientist
Luis Alberto Campos Prieto Postdoctoral scientist
Marta Jiménez González Postdoctoral scientists
Nicola D’Amelio Postdoctoral scientists
Milagros Castellanos Molina Postdoctoral scientists
Pilar López Navajas Postdoctoral scientists
Jörg Schönfelder Predoctoral student
Rajendra Sharma Predoctoral student
Francisco Ramos Predoctoral student
Ignacio Torres Rodríguez Laboratory manager

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