Predicting the Effect of Mutations on Protein-Protein Binding Interactions through Structure-Based Interface Profiles
Fig 1
Pipeline of BindProf for predicting protein-binding affinity using features derived from interface structural profiles, wild type (WT) and mutant sequences, and physics based scoring of the structures of the WT and mutant complexes.
(1) Interface profile scores and Interface profile scores features are derived by profile scoring structural alignment of structurally similar interface using an interface similarity cutoff to define the aligned sequences that are used to build the profile. (2) Physics based scores are formed at the residue or atomic level formed by modeling the mutant monomeric protein and complex and evaluating the difference in energy. (3) Sequence features are formed by the difference between the WT and mutant sequences in the number of hydrophobic (V, I, L, M, F, W, or C), aromatic (Y, F, or W), charged (R, K, D, or E), hydrogen bond acceptors (D, E, N, H, Q, S, T, or Y), and hydrogen bond donating residues (R, K, W, N, Q, H, S, T, or Y) along with the difference in amino acid volume calculated from the sequence.