High-accuracy prediction of transmembrane inter-helix contacts and application to GPCR 3D structure modeling.

ABSTRACT:

Motivation

Residue-residue contacts across the transmembrane helices dictate the three-dimensional topology of alpha-helical membrane proteins. However, contact determination through experiments is difficult because most transmembrane proteins are hard to crystallize.

Results

We present a novel method (MemBrain) to derive transmembrane inter-helix contacts from amino acid sequences by combining correlated mutations and multiple machine learning classifiers. Tested on 60 non-redundant polytopic proteins using a strict leave-one-out cross-validation protocol, MemBrain achieves an average accuracy of 62%, which is 12.5% higher than the current best method from the literature. When applied to 13 recently solved G protein-coupled receptors, the MemBrain contact predictions helped

SUBMITTER: Yang J 

PROVIDER: S-EPMC3789543 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature