The energy of formation of internal loops in triple-helical collagen polypeptides.
The sequence-dependent local destabilization in the interior of the collagen triple helix has been evaluated by means of conformational energy computations. Using a model poly(Gly-Pro-Pro) triple helix as the reference state, a method was developed for generating local loops, i.e., internal deformations, and analyzing their conformations. A seven-residue Gly-Pro-Pro- Gly-Pro-Pro-Gly fragment was replaced by the Gly-Pro-Ala-Gly-Ala-Ala-Gly sequence in one, two, or all three of the strands of the loop region. A set of loop conformations was generated in which the ends of the loop were initially fixed in the triple-helical structure. The potential energy of the entire deformed triple helix was then minimized, resulting in a variety of structures that contained deformed loops. The conformations of the triple helices at the two ends of the loops remained essentially unchanged in many of the low-energy conformations. In numerous high-energy conformations, however, the triple-helical segments were also partially or totally disrupted. The minimum-energy conformations of the whole structures were compared in terms of rms deviations of atomic coordinates with respect to the original triple helix, and of the shapes of the loops (using a distance function derived from differential geometry). Three new geometrical parameters-stretch S, kink K, and unwinding U-were defined to describe the changes in the overall orientation of the triple helices at the two ends of the loop. It is shown that, when the number of Pro residues in a short fragment is reduced, the triple helical structure can accomodate internal loops (i.e., distortions) within a 5 kcal/mol cutoff from the essentially unperturbed triple helical structure. For structures with a Gly-Pro-Ala-Gly-Ala-Ala-Gly sequence in all three strands, the probability of finding conformations with internal loops is small, i.e., 0.06. Internal loops affect the overall orientation of these structures, as measured by the helix-distortion parameters S, K, and U.
Paterlini
M G
MG
Department of Biomathematical Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
Némethy
G
G
Scheraga
H A
HA
D000595:Amino Acid Sequence; D003094:Collagen / Q000737:chemistry*; D046911:Macromolecular Substances; D008958:Models, Molecular; D008961:Models, Structural; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D046911:Macromolecular Substances; D010446:Peptide Fragments; D003094:Collagen