Levinthal Paradox
By Levinthal's paradox rewrote Cyrus Levinthal that in the molecular biology unsolved problem, clarifying the process by which an amino acid chain in a short time their functional folded state as a protein found.
description of the problem
The background to the problem is the combinatorial multitude of possible folds of a protein, which increases exponentially with the length of the amino acid chain . Even if each amino acid residue could only assume 2 states, there would be possible folding variants with a protein length of n amino acids . Would a change in conformation about need seconds, a 150 amino acids long needed protein , ie over years to find out all possible conformations the optimal (see time complexity ).
In fact, the physiologically folded native form is usually taken quickly, in fractions of a second to minutes, and proteins often only have a half-life of a few hours to days. The folding cannot be explained by randomly trying out all the possibilities. Rather, there are natural mechanisms that promote optimal folding.
Importance in bioinformatics
The problem of this “combinatorial explosion” also arises when simulating or calculating the protein structure in silico , i.e. in bioinformatics . What is known so far about the mechanisms of protein folding cannot yet be used to simulate the folding. Therefore, in a simulation, essentially all possible conformations have to be calculated. The one with the lowest energy state is selected.
Importance for protein formation
The Levinthal Paradox was formulated to illustrate the complexity of protein folding in an educational way. It is based on the assumption that the complete amino acid chain only searches for its physiological three-dimensional form after it has been completely synthesized, namely by trying out a myriad of possible conformations. In fact, during protein biosynthesis on the ribosome , each chain link adopts the energetically most favorable spatial direction after inclusion in the sequence of the extended peptide , for which the time until the next is added is sufficient. Adjacent sequence sections fold spontaneously into stable secondary structures and structural parts of smaller domains .
Supporting mechanisms can accompany the folding process, e.g. a. Folding helper proteins, molecular chaperones and “folding cores” (stable, smaller associations of structural elements that fold quickly and pull the rest of the structure into an energy minimum, i.e. the correct structure “collapses” onto the folding core). But non-physiological "helpers" can also get involved, e. B. Prions .