Computational Study of the Thermodynamics and Stability of Two Trp-Cage Miniprotein Sequences

Abstract

The Trp-Cage is widely considered to be a model system to in the field of protein folding. The folded structure of the TC10b Trp-Cage miniprotein has been experimentally shown to be more stable than that of the most commonly investigated variant, TC5b, yet remains almost unstudied in comparison. In this study, we seek to computationally verify and understand the greater stability of the TC10b Trp-Cage miniprotein through the use of replica exchange molecular dynamics (REMD) simulations. Furthermore, we seek to compare directly with experiment through the use of charged ends as opposed to the capped, neutral ends commonly used in simulations. While the difference in amino acid sequences yields a greater stability for the folded structure, the additional charges create stable charge-charge interactions for various configurations present in the unfolded state. Furthermore, the dominant charge interactions governing the folding kinetics differ from TC10b to TC5b. Due to these charge differences, we notice a longer equilibration time for TC10b as opposed to TC5b.Based on this result we speculate that the folding time of TC10b is slower than for the fast folding Tc5b sequence.