par Janin, Joël;Wodak, Shoshana 
Référence Biopolymers, 24, 3, page (509-526)
Publication Publié, 1985
Référence Biopolymers, 24, 3, page (509-526)
Publication Publié, 1985
Article révisé par les pairs
| Résumé : | We perform a computer simulation of the quaternary structure change during the allosteric transition of hemoglobin. The simulation is based on a docking procedure by which αβ dimers of human hemoglobin are associated into tetramers after being rotated in various orientations. The stability of tetramers thus reconstituted is estimated from the values of a simplified energy function describing nonbonded interactions and from the area of the surface buried in dimer–dimer contacts (their interface area), which we take to represent stabilizing interactions and solvent contribution. A systematic analysis of tetramers reconstituted with twofold symmetry reveals that when the dimers have the R tertiary structure, only tetramers having R‐like quaternary structures are stable. When the dimers have the T tertiary structure, they may associate into T‐like tetramers or a variety of quaternary structures ranging from T to near R, thus tracing a plausible reaction pathway for the allosteric transition. We subject intermediates of this pathway to energy refinement with rigid αβ dimers. The refinement demonstrates that symmetrical structures are more stable than non symmetrical ones. A detailed analysis of dimer–dimer contacts in intermediates shows how close packing is maintained over large interfaces throughout the quaternary structure change, especially in the “switch region” of contact between the C helix of α‐chains and the FG corner of β‐chains. Copyright © 1985 John Wiley & Sons, Inc. |
