title: Correlating protein hot spot surface analysis using ProBiS with simulated free energies of protein-protein interfacial residues.
abstract: A protocol was developed for the computational determination of the contribution of interfacial amino acid residues to the free energy of protein-protein binding. Thermodynamic integration, based on molecular dynamics simulation in CHARMM, was used to determine the free energy associated with single point mutations to glycine in a protein-protein interface. The hot spot amino acids found in this way were then correlated to structural similarity scores detected by the ProBiS algorithm for local structural alignment. We find that amino acids with high structural similarity scores contribute on average -3.19 kcal/mol to the free energy of protein-protein binding and are thus correlated with hot spot residues, while residues with low similarity scores contribute on average only -0.43 kcal/mol. This suggests that the local structural alignment method provides a good approximation of the contribution of a residue to the free energy of binding and is particularly useful for detection of hot spots in proteins with known structures but undetermined protein-protein complexes.
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
authors.forename: Nejc
authors.initials: N
authors.lastname: Carl
authors.forename: Milan
authors.initials: M
authors.lastname: Hodošček
authors.forename: Blaž
authors.initials: B
authors.lastname: Vehar
authors.forename: Janez
authors.initials: J
authors.lastname: Konc
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Brooks
authors.forename: Dušanka
authors.initials: D
authors.lastname: Janežič
mesh_terms: D000465:Algorithms; D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry*; D001665:Binding Sites; D030562:Databases, Protein; D019277:Entropy; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry*; D012984:Software; D040681:Structural Homology, Protein; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D011506:Proteins