Conformational flexibility of the leucine binding protein examined by protein domain coarse-grained molecular dynamics
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- 作者：Iwona Siuda (1)
Lea Th?gersen (1) (2) - 关键词：Coarse ; graining ; domELNEDIN ; Elastic network ; ELNEDIN ; LBP ; MARTINI
- 刊名：Journal of Molecular Modeling
- 出版年：2013
- 出版时间：November 2013
- 年：2013
- 卷：19
- 期：11
- 页码：4931-4945
- 全文大小：
- 作者单位：Iwona Siuda (1)
Lea Th?gersen (1) (2)
1. Centre for Membrane Pumps in Cells and Disease, Danish National Research Foundation, Bioinformatics Research Centre, Aarhus University, C. F. M?llers Alle 8, DK-8000, Aarhus C, Denmark
2. CLC bio, Silkeborgvej 2, DK-8000, Aarhus C, Denmark - ISSN：0948-5023
文摘
Periplasmic binding proteins are the initial receptors for the transport of various substrates over the inner membrane of gram-negative bacteria. The binding proteins are composed of two domains, and the substrate is entrapped between these domains. For several of the binding proteins it has been established that a closed-up conformation exists even without substrate present, suggesting a highly flexible apo-structure which would compete with the ligand-bound protein for the transporter interaction. For the leucine binding protein (LBP), structures of both open and closed conformations are known, but no closed-up structure without substrate has been reported. Here we present molecular dynamics simulations exploring the conformational flexibility of LBP. Coarse grained models based on the MARTINI force field are used to access the microsecond timescale. We show that a standard MARTINI model cannot maintain the structural stability of the protein whereas the ELNEDIN extension to MARTINI enables simulations showing a stable protein structure and nanosecond dynamics comparable to atomistic simulations, but does not allow the simulation of conformational flexibility. A modification to the MARTINI-ELNEDIN setup, referred to as domELNEDIN, is therefore presented. The domELNEDIN setup allows the protein domains to move independently and thus allows for the simulation of conformational changes. Microsecond domELNEDIN simulations starting from either the open or the closed conformations consistently show that also for LBP, the apo-structure is flexible and can exist in a closed form. Figure Closed and open conformations of the Leucine Binding Protein. Thin gray lines show the elastic network maintaining tertiary structure in coarse grained (CG) simulations. Red lines show elastic network bonds present in the ELNEDIN CG model, but removed in the domELNEDIN CG model, to allow for free protein domain motion