Effects of modulating subregions of the ANK proteins interface. (A) The folding rates of various ANK5 systems with different strengths of a specified group of contacts, normalized by the folding rate of the unmodified ANK5 system. The internal-repeat contacts (intracontacts, in cyan), the interfacial contacts (intercontacts, in green), or a subset of the interfacial contacts (interhelices and interloops, in yellow and in red, respectively) were separately modified by altering their strength to 50%, 75%, and 150% of the original value. Values above the dashed line indicate a relative acceleration. (B) The PMF of various ANK5 systems (i.e., the unmodified ANK5 and the systems with four different sets of contacts whose strength was reduced by 50%). (C) The average number of contacts that are formed at the interface and internally as a function of the total number of contacts formed during simulation time. We plot the average number of contacts at the interface between repeats i and I + 1 (thick line), at the interface formed between repeats i and i − 1 (thin line), and the internal contacts within repeat i (dashed line). We plot these curves for the ANK5 systems in which the interfacial contacts that reside between loops (green) or between helices (orange) were reduced by 50%.