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In-Depth Information
Chapter 6
Geometry and Topology of Folding Landscapes
Lorenzo Bongini
1
and Lapo Casetti
1;2
1
Dipartimento di Fisica and Centro per lo Studio delle Dinamiche Complesse
(CSDC), Universita di Firenze, via G. Sansone,
1, 50019 Sesto Fiorentino (FI), Italy
2
INFN, Sezione di Firenze, Italy
6.1. Introduction
Protein folding is one of the most fundamental and challenging open questions
in molecular biology. Proteins are polymers made of aminoacids and since the
pioneering experiments by Annsen and coworkers [1] it has been known that the
sequence of aminoacids|also called the primary structure of the protein|uniquely
determines its native state, or tertiary structure, i.e., the compact conguration the
protein assumes in physiological conditions and which makes it able to perform its
biological tasks [2]. To understand how the information contained in the sequence
is translated into the three-dimensional native structure is the core of the protein
folding problem, and its solution would allow one to predict a protein's structure
from the sole knowledge of the aminoacid sequence: being the sequencing of a
protein much easier than experimental determination of its structure, it is easy to
understand the impact such a solution would have on biochemistry and molecular
biology. Despite many remarkable advances in the last decades, the protein folding
problem is still far from a general solution [2].
A polymer made of aminoacids is referred to as a polypeptide. However, not all
polypeptides are proteins: only a very small subset of all the possible sequences of
the twenty naturally occurring aminoacids have been selected by evolution. Accord-
ing to our present knowledge, all the naturally selected proteins fold to a uniquely
determined native state, but a generic polypeptide does not (it rather has a glassy-
like behavior). Then the following question naturally arises: what makes a protein
dierent from a generic polypeptide? or, more precisely, which are the properties
a polypeptide must have to behave like a protein, i.e., to fold into a unique native
state regardless of the initial conditions, when the environment is the correct one?
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