Seminar by Juan Cortés, LAAS-CNRS, Toulouse, France
Title: Several stories about tripeptides: basic components for modeling flexible protein structures
From a mechanical point of view, fragments of three consecutive amino acid residues (called tripeptides hereafter) are very interesting elements of polypeptide chains. Indeed, if we consider the bond torsion angles as the main degrees of freedom, the 6 angles in a tripeptide (3 pairs of phi-psi angles, neglecting the variation of omega angles) are the minimal number allowing full relative mobility of the two ends of the chain. Besides, using techniques originating from robotics, the angle values corresponding to a given pose of the two ends the can be obtained very efficiently. This property has been exploited over decades within conformational sampling methods applied to cyclic peptides or protein loops. It can also be used to enhance conformational sampling of globular proteins using Monte Carlo methods, or to conceive sophisticated algorithms for modeling large-amplitude conformational transitions. In the first part of my presentation, I will briefly talk about all these applications.
Tripeptides are also interesting elements from a structural point of view. They are minimalistic fragments capturing local, sequence-dependent structural preferences of proteins. To encode and to analyze these structural properties, we have constructed an exhaustive database to tripeptide conformations extracted from experimentally-determined high-resolution protein structures. In the second part of the talk, I will show how this database can be used to construct realistic models of intrinsically disordered proteins (IDPs) and to predict the propensity of some regions to form secondary structure elements.