Computational Analysis of the Binding Specificities of PH Domains

• DOI: 10.1155/2015/792904
• Publication Date: 2015-12-31T16:05:10Z
• Authors: Zhi Jiang; Zhongjie Liang; Bairong Shen; Guang Hu
• Keywords: Models, Molecular; 0301 basic medicine; 03 medical and health sciences; Molecular Sequence Data; Static Electricity; Intracellular Signaling Peptides and Proteins; Amino Acid Sequence; Hydrophobic and Hydrophilic Interactions; Sequence Alignment; Research Article; Protein Binding; Protein Structure, Tertiary

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.