RESUMO
Three-dimensional structure modeling from maps is an indispensable step for studying proteins and their complexes with cryogenic electron microscopy. Although the resolution of determined cryogenic electron microscopy maps has generally improved, there are still many cases where tracing protein main chains is difficult, even in maps determined at a near-atomic resolution. Here we developed a protein structure modeling method, DeepMainmast, which employs deep learning to capture the local map features of amino acids and atoms to assist main-chain tracing. Moreover, we integrated AlphaFold2 with the de novo density tracing protocol to combine their complementary strengths and achieved even higher accuracy than each method alone. Additionally, the protocol is able to accurately assign the chain identity to the structure models of homo-multimers, which is not a trivial task for existing methods.
Assuntos
Aprendizado Profundo , Microscopia Crioeletrônica/métodos , Modelos Moleculares , Proteínas/química , Microscopia Eletrônica , Conformação ProteicaRESUMO
Structure modeling from maps is an indispensable step for studying proteins and their complexes with cryogenic electron microscopy (cryo-EM). Although the resolution of determined cryo-EM maps has generally improved, there are still many cases where tracing protein main-chains is difficult, even in maps determined at a near atomic resolution. Here, we have developed a protein structure modeling method, called DeepMainmast, which employs deep learning to capture the local map features of amino acids and atoms to assist main-chain tracing. Moreover, since Alphafold2 demonstrates high accuracy in protein structure prediction, we have integrated complementary strengths of de novo density tracing using deep learning with Alphafold2's structure modeling to achieve even higher accuracy than each method alone. Additionally, the protocol is able to accurately assign chain identity to the structure models of homo-multimers.