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>