Effect of conformation sampling strategies in genetic algorithm for multiple protein docking

Macromolecular protein complexes play important roles in a cell and their tertiary structure can help understand key biological processes of their functions. Multiple protein docking is a valuable computational tool for providing structure information of multimeric protein complexes. In a previous study we developed and implemented an algorithm for this purpose, named Multi-LZerD. This method represents a conformation of a multimeric protein complex as a graph, where nodes denote subunits and each edge connecting nodes denotes a pairwise docking conformation of the two subunits. Multi-LZerD employs a genetic algorithm to sample different topologies of the graph and pairwise transformations between subunits, seeking for the conformation of the optimal (lowest) energy. In this study we explore different configurations of the genetic algorithm, namely, the population size, whether to include a crossover operation, as well as the threshold for structural clustering, to find the optimal experimental setup.

Multi-LZerD was executed to predict the structures of three multimeric protein complexes, using different population sizes, clustering thresholds, and configurations of mutation and crossover. We analyzed the impact of varying these parameters on the computational time and the prediction accuracy.

Given that computational resources is a key for handling complexes with a large number of subunits and also for computing a large number of protein complexes in a genome-scale study, finding a proper setting for sampling the conformation space is of the utmost importance. Our results show that an excessive sampling of the conformational space by increasing the population size or by introducing the crossover operation is not necessary for improving accuracy for predicting structures of small complexes. The clustering is effective in reducing redundant pairwise predictions, which leads to successful identification of near-native conformations.