FMAP

FMAP models thermodynamics-based α-helix formation and stability of membrane-associated peptides in micelles, lipid bilayers, and single-pass transmembrane (TM) proteins.

Key Features:

• Helix identification and 3D modeling: Identifies potential α-helix locations in peptide sequences and generates three-dimensional models of these helices within planar bilayers and spherical micelles while estimating thermodynamic stability and tilt angles under varying temperature and pH.
• Validation datasets: Validated on 723 peptides (926 data points) across environments and on 170 single-pass TM proteins with known crystal structures.
• Accuracy and residue-level metrics: Detects over 95% of experimentally observed α-helices with average helix-end errors of approximately 2 residues (water), 3 (micelles), 4 (bilayers), and 5 (TM proteins), and residue-state prediction accuracies of 0.86–0.96 with Matthews correlation coefficients of 0.64–0.88.
• Reproduction of experimental energetics and orientation: Reproduces micelle- and membrane-binding energies with RMSD ≈2 kcal/mol and peptide tilt angles with RMSD ≈7°.
• Modeling structural polymorphism: Models structural polymorphism of membrane-binding peptides including antimicrobial, cell-penetrating, and fusion peptides.
• TM versus non-TM state prediction: Reproduces transmembrane (TM) and non-transmembrane (non-TM) states of hydrophobic and pH-triggered α-helical peptides across different lipid bilayers in over 95% of cases.

Scientific Applications:

• Structural dynamics and peptide–lipid interactions: Provides insight into α-helical structural dynamics and interactions of peptides with lipid environments.
• Mechanistic studies of peptide function: Supports investigation of mechanisms underlying antimicrobial activity, cellular penetration, and membrane fusion.
• Energetics and orientation analysis: Enables quantitative analysis of micelle- and membrane-binding energetics and peptide tilt orientations.
• Membrane insertion and state classification: Aids classification of TM versus non-TM states and assessment of membrane insertion propensity for hydrophobic and pH-triggered peptides across bilayers.

Methodology:

Thermodynamics-based molecular modeling that identifies potential α-helices, generates three-dimensional models in planar bilayers and spherical micelles, and estimates thermodynamic stability and tilt angles, reproducing micelle- and membrane-binding energies and tilt angles.