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Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
63
30-POS
Board 30
Application of Internal Normal Mode Analysis to the Study of Protein Flexibility
Elisa Frezza
, Richard Lavery.
CNRS/ Univ. Lyon I, LYON, France.
Normal mode analysis provides information on the equilibrium modes accessible to a system,
within a harmonic approximation. It has been used for several decades in studying classical
physical phenomena, as well as the flexibility of proteins. In the past decade it has also become a
tool for exploring functional motions and it has been demonstrated that low frequency motions
play an important role in biological processes. We have carried out normal mode analyses with
two different strategies depending on the choice of the independent variables: either considering
Cartesian (CCS) or internal (ICS) coordinates. The latter is advantageous since it leads to an
important reduction in the number of variables (by freezing higher-frequency bond and angle
deformations) and by extending the range over which the conformational energy hypersurface
can be assumed to be harmonic. In the case of N bodies, inter-bond distances and angles have to
be taken into account. Despite the advantages coming from the use of ICS, a transformation to
CCS is often useful to gain insight into the overall structural changes occurring in the system.
This transformation must be made so that the ICS dynamics reflect only internal motions of the
molecules and no external (overall translational or rotational) motions are introduced. We have
applied internal coordinate normal mode analysis (iNMA) to a systematic investigation of the
changes in protein conformation upon binding either another protein or a small ligand, using
different protein representations. We have also compared the flexibility deduced from normal
modes with all-atom molecular dynamics simulations. iNMA is shown to be a effective and fast
tool for predicting large conformational changes and for providing information on the key
torsions involved in the global movements.
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