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Modeling of PH Domains and Phosphoinositides Interactions and Beyond

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Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1111)

Abstract

Pleckstrin homology (PH) domains form a large family of protein modules within membrane-targeting domains. PH domains can function as lipid-binding modules, and in particular bind with different specificities and affinities to phosphoinositides (PIs). Understanding the association of PH domains to PIs is critical for many aspects of cellular biology. Bioinformatics and computational modeling approaches have become standard tools to study the structure and dynamics of PH domains and PIs. In this review, recent advances in the binding specificity of PH domains and their interactions with PIs, using bioinformatics tools for the prediction of PIs binding sites, performing molecular dynamics simulations to study PH domains-PIs interactions, as well as the computational inhibitor design for PH domains guided signaling pathways have been discussed.

Keywords

Protein-lipid interactions Drug design Signaling pathway Bioinformatics Molecular dynamics 

Abbreviations

PtdIns(4)P

Phosphatidylinositol 4-phosphate

PtdIns(3,4)P2

Phosphatidylinositol 3,4-bisphosphate

PtdIns(3,5)P2

Phosphatidylinositol 3,5-bisphosphate

PtdIns(4,5)P2

Phosphatidylinositol 4,5-bisphosphate

PtdIns (3,4,5)P3

Phosphatidylinositol 3,4,5-triphosphate;

PtdIns(1,3,4,5)P4

Phosphatidylinositol 1,3,4,5-trisphosphate

Ins (4, 5)P2

Inositol 4,5-bisphosphate

Ins(1,4,5)P 3

Inositol 1,4,5-trisphosphate

Ins(1,3,4,5)P4

Inositol 1,3,4,5-tetrakisphosphate

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Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (61401068), the China Postdoctoral Science Foundation (2016 M590495), Jiangsu College Natural Science Research Key Program (17KJA520004), and the Jiangsu Planned Projects for Postdoctoral Research Funds (1601168C).

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.School of Biology and Basic Medical Sciences, Medical CollegeSoochow UniversitySuzhouChina
  2. 2.School of Radiation Medicine and ProtectionSoochow UniversitySuzhouChina
  3. 3.Cambridge-Suda (Cam-SU) Genomic Resource CenterSoochow UniversitySuzhouChina
  4. 4.School of Electronic EngineeringUniversity of Electronic Science and Technology of ChinaChengduChina
  5. 5.Center for Systems BiologySoochow UniversitySuzhouChina

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