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Minimum energy conformations of proline-containing helices
A Polinsky1, M Goodman, K A Williams
1Department of Chemistry, University of California-San Diego, La Jolla 92093.
Biopolymers
|April 1, 1992
Summary
Membrane-bound proline residues can induce structural changes in alpha-helices, facilitating protein function. Computer modeling shows proline enables distinct conformational states, crucial for membrane protein dynamics.
Area of Science:
- Biophysics
- Computational Biology
- Structural Biology
Background:
- Proline (Pro) is often found in transmembrane alpha-helices, despite a preference for non-helical, hydrophilic environments.
- This unusual placement suggests a functional role for membrane-buried proline, potentially involving helix destabilization or structural discontinuity.
Purpose of the Study:
- To investigate the conformational flexibility of proline within a model transmembrane alpha-helix.
- To examine the energetic feasibility of proline-mediated conformational transitions in a low-polarity environment.
Main Methods:
- Computer modeling of a model transmembrane alpha-helix: (Ala)8-Leu-Pro-Phe-(Ala)8.
- Exploration of cis and trans proline conformations by randomizing key torsion angles.
- Minimization of generated conformations and organization into low-energy families.
Main Results:
- The Trans-I conformation, featuring a kinked alpha-helix at proline, was the most populated low-energy state.
- Other energetically competitive trans (Trans-II, Trans-III) and cis (Cis-I) conformations were identified.
- Conformational interconversions between trans states are possible via single torsion angle changes and minor hydrogen bond rearrangements.
Conclusions:
- Membrane-embedded proline can serve as a structural pivot, enabling transitions between distinct alpha-helical conformations.
- These proline-induced structural dynamics in a nonpolar environment are fundamental to membrane protein function.