I-TASSER (Iterative Threading ASSEmbly Refinement)

When a user submits an amino acid sequence, the server first tries to retrieve template proteins of similar folds (or super-secondary structures) from the PDB library by LOMETS (Local Meta-Threading-Server).

In the second step, the continuous fragments excised from the PDB templates are reassembled into full-length models by replica-exchange Monte Carlo simulations with the threading unaligned regions (mainly loops) built by ab initio modeling. In cases where no appropriate template is identified by LOMETS, I-TASSER will build the whole structures by ab initio modeling. The low free-energy states are identified by SPICKER through clustering the simulation decoys.

In the third step, the fragment assembly simulation is performed again starting from the SPICKER cluster centroids, where the spatial restrains collected from both the LOMETS templates and the PDB structures by TM-align are used to guide the simulations. The purpose of the second iteration is to remove the steric clash as well as to refine the global topology of the cluster centroids. The decoys generated in the second simulations are then clustered and the lowest energy structures are selected. The final full-atomic models are obtained by REMO which builds the atomic details from the selected I-TASSER decoys through the optimization of the hydrogen-bonding network.