TMPfold: A Web Tool for Predicting Stability of Transmembrane α-Helix Association.

Andrei L Lomize, Kevin A Schnitzer, Irina D Pogozheva

Journal: Journal of molecular biology 2020;432(11):3388-3394

PMID: 31682836

Full Text on Elsevier Science View on PubMed

Abstract

Estimating energies of transmembrane (TM) α-helix association is essential for understanding folding of membrane proteins and formation of their functional assemblies. A new physics-based method was developed and implemented in the TMPfold web server for the calculation of the free energy of TM helix association (ΔG) in TM α-bundles of known structure. The method was verified using the experimental ΔG values for 36 TM complexes, including dimers of 10 glycophorin A mutants. The calculated free energy changes (ΔΔG) caused by mutations in TM helices correlated with experimental changes in the stability of 42 mutants of bacteriorhodopsin and 25 mutants of rhomboid protease. TMPfold was applied for evaluation of ΔG in 554 PDB structures of 85 seven-helical TM proteins and identification of stable two-helical folding intermediates. The proposed tentative paths of cotranslational helix assembly of several polytopic proteins were consistent with experimental studies of their folding. TMPfold is accessible at (https://opm.phar.umich.edu/tmpfold_server).

Address: Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, 428 Church St., Ann Arbor, MI 48109-1065, USA. Electronic address: [email protected].; Department of Electrical Engineering and Computer Science, College of Engineering, University of Michigan, 1221 Beal Ave, Ann Arbor, MI 48109-2102, USA.; Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, 428 Church St., Ann Arbor, MI 48109-1065, USA.

DOI: 10.1016/j.jmb.2019.10.024

Link outs

Free resources

Miscellaneous:

https://assays.cancer.gov/non-CPTAC-3636

Subscription / membership required

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S0022...

MeSH Terms: Amino Acid Sequence, Humans, Internet, Protein Conformation, alpha-Helical, Protein Folding, Protein Structure, Secondary, Proteins, Software