Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

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. Levitt,M. et al. J.Mol.Biol. 1985,181,423. Sunada,S. and Go,N. J.Comput.Chem. 1984,16,328

63