Modeling Structural and Genomic Constraints in the Evolution of Proteins - Computational Modeling of Biological Systems - page 342

of disordered proteins modulates their size [ 86 ] and their conformation. It will be
interesting in the future to model protein evolution in such a way that disordered
proteins naturally arise at one side of the flexibility versus stability spectrum.

11 Conclusions

Although the models presented in this section still have a very limited ability to
represent some crucial aspects of the protein world, such as function, dynamics,
disorder, and the complexity of molecular dynamics, in our opinion they clearly
show that folding stability, both against unfolding and against misfolding, represents
a useful proxy of the genotype to phenotype relationship in proteins, and it
allows for rationalization of some important aspects of their molecular evolution
while, on the other hand, evolution is an essential ingredient for understanding the
thermodynamic properties of natural proteins.

Acknowledgments We gratefully acknowledge our past and present collaborators in this field:
David Abia, LLoyd Demetrius, Miriam Fritsche, Raul Mendez, Gonzalo S. Nido, Jonas Minning,
Alberto Pascual-Garcıa, H. Eduardo Roman, Christoph Schmitt, Stefanie Sammet, Florian
Teichert, and Michele Vendruscolo. Our research has been funded by several agencies over
the years, and we wish to specifically mention financial support by the Spanish Science and
Innovation Ministry (“Ramon y Cajal” and “Acciones Integradas Espana-Alemania” programs),
the Deutscher Akademischer Austauschdienst (“Acciones Integradas Espa na-Alemania” program)
and the Deutsche Forschungsgemeinschaft (Normalverfahren and Heisenberg program).

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