Improving AlphaFold Predicted Contacts for Alpha-Helical Transmembrane Proteins Using Structural Features.

Residue contact maps provide a condensed two-dimensional representation of three-dimensional protein structures, serving as a foundational framework in structural modeling but also as an effective tool in their own right in identifying inter-helical binding sites and drawing insights about protein function. Treating contact maps primarily as an intermediate step for 3D structure prediction, contact prediction methods have limited themselves exclusively to sequential features. Now that AlphaFold2 predicts 3D structures with good accuracy in general, we examine (1) how well predicted 3D structures can be directly used for deciding residue contacts, and (2) whether features from 3D structures can be leveraged to further improve residue contact prediction.

Improving AlphaFold predicted contacts in alpha-helical transmembrane proteins structures using structural features.

Background: Residue contacts maps offer a 2-d reduced representation of 3-d protein structures and constitute a structural constraint and scaffold in structural modeling. In addition, contact maps are also an effective tool in identifying interhelical binding sites and drawing insights about protein function. While most works predict contact maps using features derived from sequences, we believe information from known structures can be leveraged for a prediction improvement in unknown structures where decent approximate structures such as ones predicted by AlphaFold2 are available.

Improving Inter-Helix Contact Prediction With Local 2D Topological Information.

Inter-helix contact prediction is to identify residue contact across different helices in α-helical integral membrane proteins. Despite the progress made by various computational methods, contact prediction remains as a challenging task, and there is no method to our knowledge that directly tap into the contact map in an alignment free manner. We build 2D contact models from an independent dataset to capture the topological patterns in the neighborhood of a residue pair depending it is a contact or not, and apply the models to the state-of-art method's predictions to extract the features reflecting 2D inter-helix contact patterns.