Preface
Proteins are at the interface between simple and complex systems as aptly synthesized some
years ago in an enlightening paper by Hans Frauenfelder and Peter Wolynes (Frauenfelder,
Hans, and Peter G. Wolynes. “Biomolecules: where the physics of complexity and simplicity
meet.” Physics Today;(United States) 47.2 (1994)). This peculiar position makes the study of
protein structure and dynamics as the most convenient vantage points were to look at all
those features like self-organization, signal/noise discrimination, specificity of interaction,
multiple equilibria that are not present in organic molecules (whose behavior can be
satisfactorily faced by standard chemo-physical approaches) and that are too difficult to
grasp and analyze in biological systems (whose behavior emerges from a nondecomposable
mixture of top-down and bottom-up regulations). It is not without meaning that one of the
most influential journals in protein science is Biophysical Chemistry that in the title embeds
the three most central fields of natural science.
The investigation in protein science stems from very reliable data coming from the
“simplicity” end (atomic coordinates of protein structures from X-ray crystallography,
chemo-physical properties of amino acid residues) and goes into the “complexity” territories
of the discrimination of relevant “signals” from thermal noise in the case of allostery or the
conundrum of the structure–function relation in natively unfolded proteins.
This creates a perfect playground to explore the “mesoscopic realm” (Laughlin, R. B.,
Pines, D., Schmalian, J., Stojkovic ´, B. P., & Wolynes, P. (2000). The middle way. Proceedings
of the National Academy of Sciences, 97(1), 32-37.) where the still largely unknown organization principles ordering the middle-scale between atoms and galaxies are hidden.
This very ambitious goal is (more or less) latent in all book chapters that rebound
around the two basic issues of “allostery” and “network” that are present in almost all the
chapter titles. These two issues are each other connected by the fact that proteins are the
most basic “machine-like” objects sharing with human-made machine the need to organize
their architecture to a purpose that pertains to a different organization layer. It is convenient
to talk of a “purpose” more than a “function” (that is present even in simpler systems) for
the same reason that differentiates an isolated piston (whose function is to transform the
energy coming from oil explosion into a rhythmic motion) from the entire car that needs to
integrate the different functions of its parts into a coherent whole. At odds with a car, a
protein accomplishes its goal (e.g., to transport oxygen from lungs to tissues along blood
flow) without a driver, thus it must take care of self-organizing according to its microenvironment (e.g., lowering its affinity constant for oxygen in the peripheral tissues and
increasing the affinity in the lungs). This implies the need of a sensor–control–effector circuit
like any self-adjusting device; these three tasks correspond to concerted changes of the
whole configuration that start from a sensor and end up at the effector that is exactly what
“allostery” is for: sensing a relevant stimulus, transporting the information across the entire
structure, and changing the configuration accordingly.
In order to do so, the protein must have a wiring architecture that allows to both
discriminate relevant signals by thermal noise (in a situation where signal-to-noise ratio is
near unity in energetic terms) and make the signal to reach the correct effector (e.g., the
active site). This wiring architecture can profitably be interpreted in terms of a “network”
whose nodes are amino acid residues and links the effective contacts between them, and the
v
Proteins are at the interface between simple and complex systems as aptly synthesized some
years ago in an enlightening paper by Hans Frauenfelder and Peter Wolynes (Frauenfelder,
Hans, and Peter G. Wolynes. “Biomolecules: where the physics of complexity and simplicity
meet.” Physics Today;(United States) 47.2 (1994)). This peculiar position makes the study of
protein structure and dynamics as the most convenient vantage points were to look at all
those features like self-organization, signal/noise discrimination, specificity of interaction,
multiple equilibria that are not present in organic molecules (whose behavior can be
satisfactorily faced by standard chemo-physical approaches) and that are too difficult to
grasp and analyze in biological systems (whose behavior emerges from a nondecomposable
mixture of top-down and bottom-up regulations). It is not without meaning that one of the
most influential journals in protein science is Biophysical Chemistry that in the title embeds
the three most central fields of natural science.
The investigation in protein science stems from very reliable data coming from the
“simplicity” end (atomic coordinates of protein structures from X-ray crystallography,
chemo-physical properties of amino acid residues) and goes into the “complexity” territories
of the discrimination of relevant “signals” from thermal noise in the case of allostery or the
conundrum of the structure–function relation in natively unfolded proteins.
This creates a perfect playground to explore the “mesoscopic realm” (Laughlin, R. B.,
Pines, D., Schmalian, J., Stojkovic ´, B. P., & Wolynes, P. (2000). The middle way. Proceedings
of the National Academy of Sciences, 97(1), 32-37.) where the still largely unknown organization principles ordering the middle-scale between atoms and galaxies are hidden.
This very ambitious goal is (more or less) latent in all book chapters that rebound
around the two basic issues of “allostery” and “network” that are present in almost all the
chapter titles. These two issues are each other connected by the fact that proteins are the
most basic “machine-like” objects sharing with human-made machine the need to organize
their architecture to a purpose that pertains to a different organization layer. It is convenient
to talk of a “purpose” more than a “function” (that is present even in simpler systems) for
the same reason that differentiates an isolated piston (whose function is to transform the
energy coming from oil explosion into a rhythmic motion) from the entire car that needs to
integrate the different functions of its parts into a coherent whole. At odds with a car, a
protein accomplishes its goal (e.g., to transport oxygen from lungs to tissues along blood
flow) without a driver, thus it must take care of self-organizing according to its microenvironment (e.g., lowering its affinity constant for oxygen in the peripheral tissues and
increasing the affinity in the lungs). This implies the need of a sensor–control–effector circuit
like any self-adjusting device; these three tasks correspond to concerted changes of the
whole configuration that start from a sensor and end up at the effector that is exactly what
“allostery” is for: sensing a relevant stimulus, transporting the information across the entire
structure, and changing the configuration accordingly.
In order to do so, the protein must have a wiring architecture that allows to both
discriminate relevant signals by thermal noise (in a situation where signal-to-noise ratio is
near unity in energetic terms) and make the signal to reach the correct effector (e.g., the
active site). This wiring architecture can profitably be interpreted in terms of a “network”
whose nodes are amino acid residues and links the effective contacts between them, and the
v