ASTRO-FOLD 2.0: an Enhanced Framework for Protein Structure Prediction.

The three-dimensional (3-D) structure prediction of proteins, given their amino acid sequence, is addressed using the first principles-based approach ASTRO-FOLD 2.0. The key features presented are: (1) Secondary structure prediction using a novel optimization-based consensus approach, (2) β-sheet topology prediction using mixed-integer linear optimization (MILP), (3) Residue-to-residue contact prediction using a high-resolution distance-dependent force field and MILP formulation, (4) Tight dihedral angle and distance bound generation for loop residues using dihedral angle clustering and non-linear optimization (NLP), (5) 3-D structure prediction using deterministic global optimization, stochastic conformational space annealing, and the full-atomistic ECEPP/3 potential, (6) Near-native structure selection using a traveling salesman problem-based clustering approach, ICON, and (7) Improved bound generation using chemical shifts of subsets of heavy atoms, generated by SPARTA and CS23D. Computational results of ASTRO-FOLD 2.0 on 47 blind targets of the recently concluded CASP9 experiment are presented.