title: Probing Oligomerized Conformations of Defensin in the Membrane.
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.
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300060, China.|Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, China.
authors.forename: Wenxun
authors.initials: W
authors.lastname: Gan
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, 94158, USA.
authors.forename: Dina
authors.initials: D
authors.lastname: Schneidman
authors.affiliation: Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300060, China.|Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Basic Science Program, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA.|Cancer and Inflammation Program, National Cancer Institute, Frederick, MD, 21702, USA.
authors.forename: Buyong
authors.initials: B
authors.lastname: Ma
authors.affiliation: Basic Science Program, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA. nussinor@helix.nih.gov.|Cancer and Inflammation Program, National Cancer Institute, Frederick, MD, 21702, USA. nussinor@helix.nih.gov.|Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Sackler Institute of Molecular Medicine, Tel Aviv University, Tel Aviv, 69978, Israel. nussinor@helix.nih.gov.
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D023082:Defensins / Q000737:chemistry*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D023082:Defensins; D008565:Membrane Proteins
keywords: Empirical scoring function; Human defensin; Membrane protein; Molecular docking; Peptide design; Protein–protein interaction