Computational Analysis of the Binding Specificities of PH Domains

BioMed Research International
Zhi JiangGuang Hu

Abstract

Pleckstrin homology (PH) domains share low sequence identities but extremely conserved structures. They have been found in many proteins for cellular signal-dependent membrane targeting by binding inositol phosphates to perform different physiological functions. In order to understand the sequence-structure relationship and binding specificities of PH domains, quantum mechanical (QM) calculations and sequence-based combined with structure-based binding analysis were employed in our research. In the structural aspect, the binding specificities were shown to correlate with the hydropathy characteristics of PH domains and electrostatic properties of the bound inositol phosphates. By comparing these structure properties with sequence-based profiles of physicochemical properties, PH domains can be classified into four functional subgroups according to their binding specificities and affinities to inositol phosphates. The method not only provides a simple and practical paradigm to predict binding specificities for functional genomic research but also gives new insight into the understanding of the basis of diseases with respect to PH domain structures.

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Citations

Apr 7, 2016·Biochimica Et Biophysica Acta·Katerina C NastouStavros J Hamodrakas
Nov 20, 2018·Molecular Oncology·Lotteke J Y M SwierJoost Kluiver
Sep 27, 2019·Journal of Cellular and Molecular Medicine·Lirong WangJunping Zhang
Mar 26, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhangyang BiWei Zhang
Mar 4, 2020·Biochimica Et Biophysica Acta. Biomembranes·Tuo-Xian TangDaniel G S Capelluto
Jul 25, 2021·International Journal of Molecular Sciences·Chiara BrulloAndrea Spallarossa
Aug 3, 2021·International Journal of Biological Macromolecules·Pooja MittalIndrakant Kumar Singh

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Methods Mentioned

BETA
NMR

Software Mentioned

SASA
MEGA6
LIGIN
InsightII

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