BCL::MP-fold: folding membrane proteins through assembly of transmembrane helices

Membrane protein structure determination remains a challenging endeavor. Computational methods that predict membrane protein structure from sequence can potentially aid structure determination for such difficult target proteins. The de novo protein structure prediction method BCL::Fold rapidly assembles secondary structure elements into three-dimensional models. Here, we describe modifications to the algorithm, named BCL::MP-Fold, in order to simulate membrane protein folding. Models are built into a static membrane object and are evaluated using a knowledge-based energy potential, which has been modified to account for the membrane environment. Additionally, a symmetry folding mode allows for the prediction of obligate homomultimers, a common property among membrane proteins. In a benchmark test of 40 proteins of known structure, the method sampled the correct topology in 34 cases. This demonstrates that the algorithm can accurately predict protein topology without the need for large multiple sequence alignments, homologous template structures, or experimental restraints.