D-I-TASSER (Deep learning-based Iterative Threading ASSEmbly Refinement) is a new method extended from I-TASSER for high-accuracy protein structure and function predictions. Starting from a query sequence, D-I-TASSER first creates multiple sequence alignments (MSAs) by DeepMSA2 via iteratively searching of genomics and metagenomics sequence databases, where inter-residue contact/distance maps and hydrogen-bond (HB) networks are generated by three complementary deep neural-network predictors from DeepPotential, AttentionPotential, and AlphaFold2 (optional in 'Advanced options'). Meanwhile, multiple template alignmens are identified from the PDB by the DeepMSA2-guided meta-threading program LOMETS3. The full-length structural models are finally constructed by iterative fragment assembly Monte Carlo simultions under the guidance of the I-TASSER force field and deep-learning contact/distance/HB restraints, where a new domain spliting and reassemly module is introduced for modelling large-size multi-domain proteins. Finally, the biological functions of the query protein are derived using the structure-based function annotation method COFACTOR. The D-I-TASSER pipeline (as 'UM-TBM') ranked as the No. 1 server in both Single-domain and Multi-domain sections in the most recent CASP15 experiment. The server is freely accessible to all users, including commercial ones. Please report problems and questions at our Discussion Board. To model Multi-chain target, please use our protein complex structure prediction server, DMFold.
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