Binary Matrix Method to Enumerate, Hierarchically Order, and Structurally Classify Peptide Aggregation

Protein aggregation is a common and complex phenomenon in biological processes, yet a robust analysis of this aggregation process remains elusive. The commonly used methods such as center-of-mass to center-of-mass (COM-COM) distance, the radius of gyration ( R g ), hydrogen bonding (HB), and solvent accessible surface area do not quantify the aggregation accurately. Herein, a new and robust method that uses an aggregation matrix (AM) approach to investigate peptide aggregation in a MD simulation trajectory is presented. An nxn wo-dimensional AM is created by using the interpeptide C α - C α cutoff distances, which are binarily encoded (0 or 1). These aggregation matrices are analyzed to enumerate, hierarchically order, and structurally classify the aggregates. Comparison of the present AM method suggests that it is superior to the HB method since it can incorporate nonspecific interactions and the R g and COM-COM methods since the cutoff distance is independent of the length of the peptide. More importantly, the present method can structurally classify the peptide aggregates, which the conventional R g , COM-COM, and HB methods fail to do. The unique selling point of this method is its ability to structurally classify peptide aggregates using two-dimensional matrices.