46
Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Session IX Abstracts
A New Approach for Exploring Free Energy Landscapes of Large Structural Changes:
Molecular Dynamics with Excited Collective Motions (MDeNM)
Mauricio G. S. Costa
1,2
, Paulo Ricardo Batista
2
, Paulo Mascarello Bisch
3
,
David Perahia
1
.
1
CNRS, Cachan, France,
2
Fundação Oswaldo Cruz, Rio de Janeiro, Brazil,
3
Universidade
Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
The lowest frequency normal modes (NM) describe the most collective motions of a molecule. A
large diversity of structural changes can be obtained by exploring the space defined by these
modes. For macromolecules or their complexes the exploration of large conformational changes
would be computationally very demanding by carrying out solely conventional molecular
dynamics (MD) simulations. I will present a new method that we developed very recently using a
combined use of NM and MD allowing an extended conformational exploration. Its principle is
based on the kinetic activation of motions along linear combinations of NMs in MD simulations
accounting for different time scales, going from pico to milliseconds. It allows the obtaining of
unbiased large scale conformational distributions for macromolecules that are necessary for a
fine description of their structural variability and preferences, as well as for getting free energy
landscapes along relevant reaction coordinates. We demonstrated the computational efficiency of
our approach compared to conventional molecular dynamics simulations, and its usefulness for
the establishment of structure, dynamics and activity relationships in macromolecules, for
performing docking simulations in which the receptor and ligand undergo large conformational
changes upon association, for understanding the dissociation processes, and for studying channel
opening in membrane proteins. I will give different examples of the application of our method.
