Ab initio construction of all-atom loop conformations.

In this study, a new ab initio method named CLOOP has been developed to build all-atom loop conformations. In this method, a loop main-chain conformation is generated by sampling main-chain dihedral angles from a restrained varphi/psi set, and the side-chain conformations are built randomly. The CHARMM all-atom force field was used to evaluate the loop conformations. Soft core potentials were used to treat the non-bond interactions, and a designed energy-minimization technique was used to close and optimize the loop conformations. It is shown that the two strategies improve the computational efficiency and the loop-closure rate substantially compared to normal minimization methods. CLOOP was used to construct the conformations of 4-, 8-, and 12-residue loops in Fiser's test set. The average main-chain root-mean-square deviations obtained in 1,000 trials for the 10 different loops of each size are 0.33, 1.27, and 2.77 A, respectively. CLOOP can build all-atom loop conformations with a sampling accuracy comparable with previous loop main-chain construction algorithms. [Figure: see text].