Finding multiple minimum-energy conformations of the hydrophobic-polar protein model via multidomain sampling

Abstract

We demonstrate the efficiency of the multidomain sampler (MDS) in finding multiple distinct global minima and low-energy local minima in the hydrophobic-polar (HP) lattice protein model. Extending the idea of partitioning energy space in the Wang-Landau algorithm, our approach introduces an additional partitioning scheme to divide the protein conformation space into local basins of attraction. This double-partitioning design is very powerful in guiding the sampler to visit the basins of unexplored local minima. An H-residue subchain distance is used to merge the basins of similar local minima into one domain, which increases the diversity among identified minimum-energy conformations. Moreover, a visit-enhancement factor is introduced for long protein chains to facilitate jumps between basins. Results on three benchmark protein sequences reveal that our approach is capable of finding multiple global minima and hundreds of low-energy local minima of great diversity.