Protein tertiary structure prediction using a branch and bound algorithm.

We report a new method for predicting protein tertiary structure from sequence and secondary structure information. The predictions result from global optimization of a potential energy function, including van der Waals, hydrophobic, and excluded volume terms. The optimization algorithm, which is based on the alphaBB method developed by Floudas and coworkers (Costas and Floudas, J Chem Phys 1994;100:1247-1261), uses a reduced model of the protein and is implemented in both distance and dihedral angle space, enabling a side-by-side comparison of methodologies. For a set of eight small proteins, representing the three basic types--all alpha, all beta, and mixed alpha/beta--the algorithm locates low-energy native-like structures (less than 6A root mean square deviation from the native coordinates) starting from an unfolded state. Serial and parallel implementations of this methodology are discussed.