The Development of Tools to Investigate Relationships between Atomic Contacts in Proteins

Abstract

The time-varying states of atomic contacts reflect the dynamics of the protein. Protein dynamics are linked to protein functions. Thus, it is crucial to have automatic methods for extracting the relationships between atomic contacts. In this study, three methods were used to extract the relationships between atomic contacts, reverse engineering based on Bernoulli mixture models (ReBmm), correlated motion, and Leader Finder. The protein used in this study was Cu/Zn superoxide dismutase (SOD1), and its aggregations is associated with amyotrophic lateral sclerosis (ALS). Its wild type (WT) form and mutant type (A4V) were simulated using all-atom molecular dynamics (MD) simulations. The results from the three methods suggested m the aggregation of SOD begins with the downward movements in the electro static loop and propagated to the Zn binding loop, and several strands of the β-sheet. As a result, the buried surface area between the front sheets and the back sheets became exposed and may be the cause of aggregation. The three methods, ReBMM, correlated motion, and Leader Finder proved to be useful tools for studying the relationship between atomic contacts in protein simulations.