Predicting the Assembly Order of Protein Complexes by Multi-Temperature Coarse-Grained Simulations

Abstract

AbstractAn increasing number of structures of protein complexes have been resolved. In addition to one or several static structures, the dynamic process of a protein complex, such as the assembly order of its protein subunits, is functionally very important. In addition to experimental techniques for studying subcomplexes in the assembly of a protein complex, computational methods can be used to predict the assembly order. Since sampling is a nontrivial issue in simulating the assembly process, coarse-grained simulations are more efficient than atomic simulations are. In this work, we developed a computational tool for predicting the disassembly and assembly order of protein complexes by coarse-grained simulations at multiple temperatures. The method was illustrated using two protein complexes, and the predicted assembly orders are consistent with available experimental data. Our studies also suggest that the assembly order of a protein complex may be determined not only by intersubunit interactions but also by the stability of the subunits.SignificanceProtein complexes play important roles in various biological processes. The order in which a protein complex is assembled is critical for its proper formation and function. In the assembly process of a complex, the precise arrangement of protein subunits determines their stability, activity and interaction partners. This work provides a computational tool for predicting the assembly order of protein complexes, with the expectation of revealing the dynamic mechanism behind the function of protein complexes.