Evolutionary dynamics of a lattice dimer: A toy model for stability vs. affinity trade-offs in proteins

Emanuele Loffredo, Elisabetta Vesconi,, Rostam Razban, Orit Peleg, Eugene Shakhnovich, Simona Cocco, Remi Monasson

Abstract:

Understanding how a stressor applied on a biological system shapes its evolution is key to achieving
targeted evolutionary control. Here we present a toy model of two interacting lattice proteins to
quantify the response to the selective pressure defined by the binding energy. We generate sequence
data of proteins and study how the sequence and structural properties of dimers are affected by the
applied selective pressure, both during the evolutionary process and in the stationary regime. In
particular we show that internal contacts of native structures lose strength, while inter-structure
contacts are strengthened due to the folding-binding competition. We discuss how dimerization is
achieved through enhanced mutability on the interacting faces, and how the designability of each
native structure changes upon introduction of the stressor.