Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

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.

116