Protein conformational spaces: sampling, measuring and clustering
Proteins are large molecules composed of linear chains of connected
aminoacids, being largely responsible for the processes taking
place in living organisms. The conformation (spatial structural
arrangment) adopted by those chains ensures the chemical and
physical properties required for proper protein functioning, with a
loss of the normal conformational features leading to malfunction
or disease. Therefore, a detailed characterization of the
distribution of conformations is determinant to understand and
rationalize the behavior of proteins. This talk discusses some
aspects and open issues in the study of protein conformational
behavior in the field of Molecular Modelling. Although
deterministic or stochastic computational methods can be used to
sample protein conformations, the sampling is often partial and
many alternative dissimilarity measures and classification
algorithms exist. Thus, questions remain about the suitability of
available measures, conformational spaces and clustering methods
for properly reflecting the underlying energetics of these
molecules and, ultimately, their thermodynamic and kinetic
properties. Overall, the viewpoint adopted in the talk is that of a
physical biochemist trying to take advantage of mathematical
methods (and hoping to get helpful suggestions from the audience).
