Amino acid function and docking site prediction through combining disease variants, structure alignments, sequence alignments, and molecular dynamics: a study of the HMG domain

BMC Bioinformatics

Proceedings

Jeremy W Prokop¹  Amy Milsted¹  Thomas C Leeper²  Zhong-Hui Duan³ 

[1] Department of Biology, Program in Integrated Bioscience, The University of Akron, Akron, OH, USA;Department of Chemistry, Program in Integrated Bioscience, The University of Akron, Akron, OH, USA;Department of Computer Science, Program in Integrated Bioscience, The University of Akron, Akron, OH, USA;

关键词: Androgen Receptor;    High Mobility Group;    Structure Alignment;    High Mobility Group Protein;    HMGB1 Protein;   

DOI  :  10.1186/1471-2105-13-S2-S3

来源: Springer

【 摘 要 】

BackgroundThe DNA binding domain of HMG proteins is known to be important in many diseases, with the Sox sub-family of HMG proteins of particular significance. Numerous natural variants in HMG proteins are associated with disease phenotypes. Integrating these natural variants, molecular dynamic simulations of DNA interaction and sequence and structure alignments give detailed molecular knowledge of potential amino acid function such as DNA or protein interaction.ResultsA total of 33 amino acids in HMG proteins are known to have natural variants in diseases. Eight of these amino acids are normally conserved in human HMG proteins and 27 are conserved in the human Sox sub-family. Among the six non-Sox conserved amino acids, amino acids 16 and 45 are likely targets for interaction with other proteins. Docking studies between the androgen receptor and Sry/Sox9 reveals a stable amino acid specific interaction involving several Sox conserved residues.ConclusionThe HMG box has structural conservation between the first two of the three helixes in the domain as well as some DNA contact points. Individual sub-groups of the HMG family have specificity in the location of the third helix, DNA specific contact points (such as amino acids 4 and 29), and conserved amino acids interacting with other proteins such as androgen receptor. Studies such as this help to distinguish individual members of a much larger family of proteins and can be applied to any protein family of interest.

【 授权许可】

CC BY   
© Prokop et al.; licensee BioMed Central Ltd. 2012