10.25376/hra.7822706.v1 Bian Li Bian Li Jeffrey L. Mendenhall Jeffrey L. Mendenhall Elizabeth Dong Nguyen Elizabeth Dong Nguyen Brian E. Weiner Brian E. Weiner Axel W. Fischer Axel W. Fischer Jens Meiler Jens Meiler Improving prediction of helix–helix packing in membrane proteins using predicted contact numbers as restraints Health Research Alliance 2019 contact number residue packing density helix–helix packing helical membrane protein de novo protein structure prediction Simulation and Modelling 2019-03-09 03:24:44 Journal contribution https://hra.figshare.com/articles/journal_contribution/Improving_prediction_of_helix_helix_packing_in_membrane_proteins_using_predicted_contact_numbers_as_restraints/7822706 <div>One of the challenging problems in tertiary structure prediction of helical membrane proteins (HMPs) is the determination of rotation of alpha-helices around the helix normal. Incorrect prediction of helix rotations substantially disrupts native residue–residue contacts while inducing only a relatively small effect on the overall fold. We previously developed a method for predicting residue contact numbers (CNs), which measure the local packing density of residues within the protein tertiary structure. In this study, we tested the idea of incorporating predicted CNs as restraints to guide the sampling of helix rotation. For a benchmark set of 15 HMPs with simple to rather complicated folds, the average contact recovery (CR) of best sampled models was improved for all targets, the likelihood of sampling models with CR greater than 20% was increased for 13 targets, and the average RMSD100 of best-sampled models was improved for 12 targets. This study demonstrated that</div><div>explicit incorporation of CNs as restraints improves the prediction of helix–helix packing.</div>