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 language||American English|
|Title of host publication||Methods in Molecular Biology|
|Publisher||Humana Press Inc.|
|Number of pages||10|
|State||Published - 2017|
|Name||Methods in Molecular Biology|
Bibliographical noteFunding Information:
The authors are funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research was funded in part by the US Army Medical Research Acquisition Activity under grant W81XWH-05-1-0002. N.Z. thanks Chinese NFSC grant 30772529 and 973 program grants 2011CB933100 and 2010CB933900.
© Springer Science+Business Media New York 2017.
- Empirical scoring function
- Human defensin
- Membrane protein
- Molecular docking
- Peptide design
- Protein–protein interaction