116
Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II
62-POS
Board 15
Solvent Accessibility Affects Binding Hot-Spots at Protein Interfaces.
Irina Moreira
.
REQUIMTE, Porto, Portugal.
Protein-protein interactions are the basis of many physiological processes and their specificity
and affinity are critically important in heath and disease. Various studies demonstrated the
existence of binding Hot-Spots (HS) at these interfaces.[1] HS are residues that potentially have
a higher contribute for the overall binding free energy and are usually surrounded by a layer of
residues (forming an O-ring structure) to better protect them from the bulk solvent. To test the
application of this theory at protein-protein and protein-DNA interfaces we have performed
Molecular Dynamic (MD) simulations of various complexes and analyzed the position and
dynamics of water molecules as well as different features of Solvent Accessible Surface Area
(SASA).[2-4] Our results clearly show a much lower number of water molecules surrounding a
HS in comparison with a non-HS and a higher loss of SASA upon complex formation in both
types of interfaces. The use of the various SASA features as HS differentiators was also
statistically evaluated and the combination of them analyzed by a support vector machine
method, which allowed us to establish a new accurate model for predicting hot-spots: SBHD
(SASA-Based Hot-Spots Detection).[5] This method presents a Precision, Recall, and F1 score
of 0.91, 0.73 and 0.81 for an independent test set.
[1] I.S. Moreira, P.A. Fernandes, M.J. Ramos, Proteins, 68 (2007) 803-812.
[2] I.S. Moreira, J.M. Martins, M.J. Ramos, P.A. Fernandes, M.J. Ramos, Biochem. Biophys.
Acta, 1834 (2013) 401-414.
[3] I.S. Moreira, R.M. Ramos, J.M. Martins, P.A. Fernandes, M.J. Ramos, Journal of
Biomolecular Structure and Dynamics, 32 (2013) 186-197.
[4] R.M. Ramos, L.F. Fernandes, I.S. Moreira, Computational Biology and Chemistry, 44 (2013)
31-39.
[5] J.M. Martins, R.M. Ramos, A.C. Pimenta, I.S. Moreira, Proteins: Structure, Function, and
Bioinformatics, 82 (2014) 479-490.
