Computational Models for the Helix Tilt Angle

The concept of hydrophobic imbalance and that of hydrophobic and hydrophilic centers are used along with side chain models in the computation of helix orientation and tilt angle in or near a membrane. Rotamer statistics are used to infer typical side chain positions and chain length for each amino acid, and the results are used in fast computation of helix orientation. Sliding windows are used to compute local tilt angles on long alpha-helices that defy idealized modeling and generate tilt angle profiles. Seven different procedures based on different formulas and hydrophobicity scales are used for comparison. These procedures generated very similar tilt angle profiles. These profiles provide insights into helix deformation, membrane destabilization, and similarity and differences between membrane proteins.

[1]  Luis Fernández Pacios,et al.  Distinct Molecular Surfaces and Hydrophobicity of Amino Acid Residues in Proteins , 2001, J. Chem. Inf. Comput. Sci..

[2]  R. Brasseur,et al.  Fusogenic Properties of the C-terminal Domain of the Alzheimer β-Amyloid Peptide* , 1996, The Journal of Biological Chemistry.

[3]  B. Peter,et al.  BAR Domains as Sensors of Membrane Curvature: The Amphiphysin BAR Structure , 2004, Science.

[4]  R. Brasseur,et al.  Tilted peptides: a motif for membrane destabilization (Hypothesis) , 2000, Molecular membrane biology.

[5]  R. Brasseur,et al.  The mode of insertion of the paramyxovirus F1 N-terminus into lipid matrix, an initial step in host cell/virus fusion , 1988, Virus Genes.

[6]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[7]  E. Goormaghtigh,et al.  Membrane helix orientation from linear dichroism of infrared attenuated total reflection spectra. , 1999, Biophysical journal.

[8]  B D Silverman,et al.  Hydrophobic moments of protein structures: Spatially profiling the distribution , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Roland L. Dunbrack,et al.  Prediction of protein side-chain rotamers from a backbone-dependent rotamer library: a new homology modeling tool. , 1997, Journal of molecular biology.

[10]  K. Takano,et al.  A new scale for side-chain contribution to protein stability based on the empirical stability analysis of mutant proteins. , 2001, Protein engineering.

[11]  B. Charloteaux,et al.  Computational study of lipid‐destabilizing protein fragments: Towards a comprehensive view of tilted peptides , 2001, Proteins.

[12]  S H White,et al.  Energetics, stability, and prediction of transmembrane helices. , 2001, Journal of molecular biology.

[13]  David Eisenberg,et al.  The helical hydrophobic moment: a measure of the amphiphilicity of a helix , 1982, Nature.

[14]  R. Epand,et al.  Oblique membrane insertion of viral fusion peptide probed by neutron diffraction. , 2000, Biochemistry.

[15]  R. Brasseur,et al.  Are the fusion processes involved in birth, life and death of the cell depending on tilted insertion of peptides into membranes? , 1999, Journal of theoretical biology.

[16]  Lukas K. Tamm,et al.  Membrane structure and fusion-triggering conformational change of the fusion domain from influenza hemagglutinin , 2001, Nature Structural Biology.