By: Leonor Cruzeiro
From: Univ. Algarve
At: Instituto de Investigação Interdisciplinar, B1-01
According to the thermodynamics hypothesis  and the associated theory of a funnel-shaped free energy landscape [2-5], the native structure of proteins is that which minimizes its free energy. In this view, the protein folding problem is essentially solved [4,5] since finding a protein structure from its sequence, in a computer, depends solely on having a sufficiently accurate potential to describe the interactions of protein atoms with one another and on the availability of enough computer power to explore the protein conformational space. A question  that lurks underneath the funnel theory is whether the potential energy functions that are successful in the modelling of proteins and of their interaction with ligands do indeed lead to a funnel-shaped free energy landscape. In this talk, evidence for a multi-funnel landscape [7,8] is presented and a new, detailed, kinetic, mechanism for protein folding is put forward that can explain both reproducible folding in a multi-funnel free energy landscape, as well as the occasional misfolding [7,8]. Finally, the talk ends with a discussion of how this new kinetic mechanism fits with the existing experimental data on protein folding and misfolding.
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