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Common Structural Features of Hydrophobic α-Helical Hot Spots: Insights for the Design of Novel α-Helix Mimetics.

ABSTRACT: The binding conformations of α-helical hydrophobic hot spots are convergent into two spatial areas in protein-protein complex structures. The physical basis for convergence was disclosed, which allows the development of pharmacophore models for i/i + 4/i + 7 or i/i + 3/i + 4 α-helical hot spots. Further investigation revealed that this convergence of binding conformations is common among all hydrophobic hot spots regardless of their α-helical positions. This observation led to a streamlined generation of pharmacophore models for hydrophobic hot spots at any positions along the α-helix. These successfully evaluated pharmacophore models may be useful for designing novel α-helical hot spot mimetics.

SUBMITTER: Kell SR

PROVIDER: S-EPMC9575182 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Common Structural Features of Hydrophobic α-Helical Hot Spots: Insights for the Design of Novel α-Helix Mimetics.

Kell Shelby R SR Wang Zhen Z Ji Haitao H

ACS medicinal chemistry letters 20220914 10

The binding conformations of α-helical hydrophobic hot spots are convergent into two spatial areas in protein-protein complex structures. The physical basis for convergence was disclosed, which allows the development of pharmacophore models for i/i + 4/i + 7 or i/i + 3/i + 4 α-helical hot spots. Further investigation revealed that this convergence of binding conformations is common among all hydrophobic hot spots regardless of their α-helical positions. ...[more]

PMID: 36262397

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