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Biophysical and Integrative Characterization of Protein Intrinsic Disorder as a Prime Target for Drug Discovery.

ABSTRACT: Protein intrinsic disorder is increasingly recognized for its biological and disease-driven functions. However, it represents significant challenges for biophysical studies due to its high conformational flexibility. In addressing these challenges, we highlight the complementary and distinct capabilities of a range of experimental and computational methods and further describe integrative strategies available for combining these techniques. Integrative biophysics methods provide valuable insights into the sequence-structure-function relationship of disordered proteins, setting the stage for protein intrinsic disorder to become a promising target for drug discovery. Finally, we briefly summarize recent advances in the development of new small molecule inhibitors targeting the disordered N-terminal domains of three vital transcription factors.

SUBMITTER: Luo S

PROVIDER: S-EPMC10046839 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Biophysical and Integrative Characterization of Protein Intrinsic Disorder as a Prime Target for Drug Discovery.

Luo Shuqi S Wohl Samuel S Zheng Wenwei W Yang Sichun S

Biomolecules 20230314 3

Protein intrinsic disorder is increasingly recognized for its biological and disease-driven functions. However, it represents significant challenges for biophysical studies due to its high conformational flexibility. In addressing these challenges, we highlight the complementary and distinct capabilities of a range of experimental and computational methods and further describe integrative strategies available for combining these techniques. Integrative biophysics methods provide valuable insight ...[more]

PMID: 36979465

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