The understating of protein folding and of protein design is made difficult by the necessity of describing proteins with a very high molecular detail. The large number of parameters involved requires massive computational resources and does not always allow for a simple understanding of the phenomena. A novel model will be introduced where a minimal set of parameters has been selected and optimized for full consistency between folding and design of real proteins. The results demonstrate that the sequences designed with our model fold to natural occurring protein structures, they have a low frustration folding free energy landscape and are very similar to the natural sequences themselves. Moreover, the folding of an extensive set of proteins has been characterized in detail showing a remarkable precision in the structural prediction power. This work is key in our effort to show that folding and design of heteropolymers is possible provided that a minimal set of geometrical constraints are present to reduce the accessible configurational space of the heteropolymers. This minimal constraint principle is not directly evident in mean field theory, and is implicit in lattice heteropolymers, however we here show that once it is satisfied it makes the design and folding predictive on a quantitative level without the need of further assumptions.

Minimum constraint principle to define quantitative models for protein folding and design

246th National Meeting (2013)

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