For distribution

[CM ICTP - Trieste]

JOINT ICTP/SISSA STATISTICAL PHYSICS SEMINAR

	

Tuesday, 8 May    -    12:30 hrs.




Seminar Room - ICTP Main Building    (first floor)

		


A. LAIO     ( SISSA - International School for Advanced Studies )



"Folding of small proteins in explicit solvent by the combined use of 
metadynamics and replica exchange"




Abstract

We recently developed a method that combines replica exchange with 
metadynamics and allows, with a moderate computational effort, the 
simultaneous reconstruction of the free energy as a function of a large 
number of variables.  This allows simulating very complex reactions, 
like protein folding, in which the reaction coordinate is totally 
unknown.  We will discuss applications of the methodology to the 
folding in explicit solvent of the TRP cage miniprotein and of the 
advillin headpiece C-terminal domain (cHP) and its Pro62Ala mutant. Our 
calculations allow,  for these small proteins, the ab initio prediction 
of the folded state.  For the advillin headpiece we find that the 
Pro62Ala mutation does not change the overall stability of the native 
state but it significantly alters the entropic contribution to the 
folding free energy. Therefore,  the mutant is still folded at room 
temperature but is characterized by a lower unfolding temperature. This 
prediction was subsequently validated by NMR and CD experiments.