biophysics Module

The biophysics module enhances synthetic structures with realistic biochemical properties, such as pH-dependent protonation and terminal capping.

Overview

While the core generator builds the 3D atomic coordinates, the biophysics module handles the "chemical identity" of the residues, ensuring that protonation states and terminal groups are biologically accurate for a given environment.

Main Functions

::: synth_pdb.biophysics.apply_ph_titration options: show_root_heading: true show_source: true

::: synth_pdb.biophysics.cap_termini options: show_root_heading: true show_source: true

::: synth_pdb.biophysics.find_salt_bridges options: show_root_heading: true show_source: true

Usage Examples

pH Titration

Apply pH-dependent protonation to residues like Histidine.

import biotite.structure as struc
from synth_pdb.biophysics import apply_ph_titration

# Load structure
# structure: struc.AtomArray

# Apply acidic pH (renames HIS to HIP)
structure = apply_ph_titration(structure, ph=5.0)

# Apply physiological pH (probabilistically renames HIS to HIE or HID)
structure = apply_ph_titration(structure, ph=7.4)

Terminal Capping

Add Acetyl (ACE) and N-Methylamide (NME) caps to the termini of a peptide fragment.

from synth_pdb.biophysics import cap_termini

# Add caps to structure
structure = cap_termini(structure)

Salt Bridge Detection

Identify potential ionic interactions between acidic and basic residues.

from synth_pdb.biophysics import find_salt_bridges

bridges = find_salt_bridges(structure, cutoff=5.0)
for b in bridges:
    print(f"Salt bridge between {b['res_ia']} and {b['res_ib']}")

Educational Notes

pH and Protonation

Biological function depends heavily on pH. The most sensitive residue near physiological pH (7.4) is Histidine ($pK_a \approx 6.0$). - pH < 6.0: The imidazole ring is protonated and carries a $+1$ charge. Represented as HIP. - pH > 6.0: The ring is neutral ($0$ charge). It exists in two tautomeric forms: HIE ($\epsilon$ nitrogen protonated) or HID ($\delta$ nitrogen protonated).

Terminal Capping

Uncapped termini ($NH_3^+$ and $COO^-$) introduce strong charges that are often unrealistic for a short peptide fragment intended to represent a region within a larger protein. - N-terminus cap (ACE): Acetyl group ($CH_3\text{-}CO\text{-}$) replaces the terminal hydrogen. - C-terminus cap (NME): N-Methylamide group ($\text{-}NH\text{-}CH_3$) replaces the terminal oxygen.

Capping eliminates these artificial terminal charges, providing a more realistic model of internal protein segments.

Salt Bridges

A salt bridge is a combination of two non-covalent interactions: Hydrogen Bonding and Electrostatic (Ionic) Attraction. It occurs between a positively charged basic residue (Lys, Arg, His) and a negatively charged acidic residue (Asp, Glu). These bridges are critical for stabilizing tertiary structure and driving specific molecular recognition.

References

  • Proline Conformation: MacArthur, M. W., & Thornton, J. M. (1991). "Influence of proline residues on protein conformation." Journal of Molecular Biology. DOI: 10.1016/0022-2836(91)90627-W
  • Salt Bridges: Bosshard, H. R., et al. (2004). "The salt bridge in proteins." Journal of Molecular Recognition. DOI: 10.1002/jmr.657
  • pH and Proteins: Tanford, C. (1962). "The interpretation of hydrogen ion titration curves of proteins." Advances in Protein Chemistry.

See Also