V. Carnevale, C. Micheletti, F. Pontiggia and R. Potestio
Bridging the Atomic and Coarse-Grained Descriptions of Collective Motions in Proteins
Chapter 7 (pages 159-178) in book: Multiscale Approaches to Protein Modeling, Springer Verlag, 2010,ISBN-10: 1441968881
ABSTRACT
Protein structures are carefully "designed" to balance the need of thermodynamical
stability with the necessity of sustaining conformational changes and
efficiently interconverting among different functionally relevant conformers. This
subtle equilibrium reverberates in the complexity of the free-energy landscape which is
endowed by a variety of local minima of varying depth and breadth corresponding
to the salient structural states of the molecules. In this chapter we will present
some concepts and computational algorithms that can be used to characterize the
internal dynamics of proteins and relate it to their "functional mechanics". We will
apply these concepts to the analysis of a molecular dynamics simulation of adenylate
kinase, a protein for which the structural rearrangement is known to be crucial
for the accomplishment of its biological function. We will show how, despite the
structural heterogeneity of the explored conformational ensemble, the generalized
directions accounting for conformational fluctuations within and across the visited
conformational substates are robust and can be described by a limited set of collective
coordinates. Finally, as a term of comparison, we will show that in the case of HIV-1
Transactivator of Transcription (TAT), a naturally unstructured protein, the lack of
any hierarchical organization of the free-energy minima results in a poor consistency
of the essential dynamical spaces sampled during the dynamical evolution of
the system.