Probing oligomerized conformations of defensin in the membrane

Wenxun Gan, Dina Schneidman, Ning Zhang, Buyong Ma, Ruth Nussinov

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Computational prediction and design of membrane protein–protein interactions facilitate biomedical engineering and biotechnological applications. Due to their antimicrobial activity, human defensins play an important role in the innate immune system. Human defensins are attractive pharmaceutical targets due to their small size, broad activity spectrum, reduced immunogenicity, and resistance to proteolysis. Protein engineering based modification of defensins can improve their pharmaceutical properties. Here we present an approach to computationally probe defensins’ oligomerization states in the membrane. First, we develop a novel docking and rescoring algorithm. Then, on the basis of the 3D structure of Sapecin, an insect defensin, and a model of its antimicrobial ion-channel, we optimize the parameters of our empirical scoring function. Finally, we apply our docking program and scoring function to the hBD-2 (human β-defensin-2) molecule and obtain structures of four possible oligomers. These results can be used in higher level simulations.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
Pages353-362
Number of pages10
DOIs
StatePublished - 2017

Publication series

NameMethods in Molecular Biology
Volume1529

Keywords

  • Empirical scoring function
  • Human defensin
  • Membrane protein
  • Molecular docking
  • Peptide design
  • Protein–protein interaction

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics

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