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Computational elucidation of membrane protein (MP) structures is challenging partially due to lack of sufficient solved structures for homology modeling. Here we describe a high-throughput deep transfer learning method that first predicts MP contacts by learning from non-membrane proteins (non-MPs) and then predicting three-dimensional structure models using the predicted contacts as distance restraints. Tested on 510 non-redundant MPs, our method has contact prediction accuracy at least 0.18 better than existing methods, predicts correct folds for 218 MPs (TMscore at least 0.6), and generates three-dimensional models with RMSD less than 4 Angstrom and 5 Angstrom for 57 and 108 MPs, respectively. A rigorous blind test in the continuous automated model evaluation (CAMEO) project shows that our method predicted high-resolution three-dimensional models for two recent test MPs of 210 residues with RMSD close to 2 Angstrom. We estimated that our method could predict correct folds for between 1,345 and 1,871 reviewed human multi-pass MPs including a few hundred new folds, which shall facilitate the discovery of drugs targeting at membrane proteins.
Computational prediction of membrane protein (MP) structures is very challenging partially due to lack of sufficient solved structures for homology modeling. Recently direct evolutionary coupling analysis (DCA) sheds some light on protein contact pre
Contact-assisted protein folding has made very good progress, but two challenges remain. One is accurate contact prediction for proteins lack of many sequence homologs and the other is that time-consuming folding simulation is often needed to predict
Exploring and understanding the protein-folding problem has been a long-standing challenge in molecular biology. Here, using molecular dynamics simulation, we reveal how parallel distributed adjacent planar peptide groups of unfolded proteins fold re
Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins. In comparis
In structure-based models of proteins, one often assumes that folding is accomplished when all contacts are established. This assumption may frequently lead to a conceptual problem that folding takes place in a temperature region of very low thermody