INVESTIGADORES
MODENUTTI Carlos Pablo
artículos
Título:
Solvent structure improves docking prediction in lectin?carbohydrate complexes
Autor/es:
GAUTO, D; PETRUK, A; MODENUTTI, C; BLANCO, J
Revista:
GLYCOBIOLOGY
Editorial:
OXFORD UNIV PRESS INC
Referencias:
Lugar: Oxford; Año: 2012
ISSN:
0959-6658
Resumen:
Recognition and complex formation between proteins and
carbohydrates is a key issue in many important biological processes.
Determination of the three-dimensional structure of
such complexes is thus most relevant, but particularly challenging
because
of their usually low binding affinity. In silico
docking methods have a long-standing tradition in predicting
protein?ligand
complexes, and allow a potentially fast exploration
of a number of possible protein?carbohydrate complex structures.
However,
determining which of these predicted complexes
represents the correct structure is not always straightforward.
In this work, we present a modification of
the scoring function provided by AutoDock4, a widely used docking
software, on
the basis of analysis of the solvent structure
adjacent to the protein surface, as derived from molecular dynamics
simulations,
that allows the definition and characterization of
regions with higher water occupancy than the bulk solvent, called water
sites. They mimic the interaction held between the
carbohydrate ?OH groups and the protein. We used this information for an
improved docking method in relation to its capacity
to correctly predict the protein?carbohydrate complexes for a number of
tested proteins, whose ligands range in size from
mono- to tetrasaccharide. Our results show that the presented method
significantly
improves the docking predictions. The resulting
solvent-structure-biased docking protocol, therefore, appears as a
powerful
tool for the design and optimization of development
of glycomimetic drugs, while providing new insights into
protein?carbohydrate
interactions. Moreover, the achieved improvement
also underscores the relevance of the solvent structure to the protein
carbohydrate
recognition process.