NDLI: Molecular dynamics simulations of the Bcl-2 protein to predict the structure of its unordered flexible loop domain

Content Provider	Springer Nature Link
Author	Raghav, Pawan Kumar Verma, Yogesh Kumar Gangenahalli, Gurudutta U.
Copyright Year	2011
Abstract	B-cell lymphoma (Bcl-2) protein is an anti-apoptotic member of the Bcl-2 family. It is functionally demarcated into four Bcl-2 homology (BH) domains: BH1, BH2, BH3, BH4, one flexible loop domain (FLD), a transmembrane domain (TM), and an X domain. Bcl-2’s BH domains have clearly been elucidated from a structural perspective, whereas the conformation of FLD has not yet been predicted, despite its important role in regulating apoptosis through its interactions with JNK-1, PKC, PP2A phosphatase, caspase 3, MAP kinase, ubiquitin, PS1, and FKBP38. Many important residues that regulate Bcl-2 anti-apoptotic activity are present in this domain, for example Asp34, Thr56, Thr69, Ser70, Thr74, and Ser87. The structural elucidation of the FLD would likely help in attempts to accurately predict the effect of mutating these residues on the overall structure of the protein and the interactions of other proteins in this domain. Therefore, we have generated an increased quality model of the Bcl-2 protein including the FLD through modeling. Further, molecular dynamics (MD) simulations were used for FLD optimization, to predict the flexibility, and to determine the stability of the folded FLD. In addition, essential dynamics (ED) was used to predict the collective motions and the essential subspace relevant to Bcl-2 protein function. The predicted average structure and ensemble of MD-simulated structures were submitted to the Protein Model Database (PMDB), and the Bcl-2 structures obtained exhibited enhanced quality. This study should help to elucidate the structural basis for Bcl-2 anti-apoptotic activity regulation through its binding to other proteins via the FLD.
Starting Page	1885
Ending Page	1906
Page Count	22
File Format	PDF
ISSN	16102940
Journal	Journal of Molecular Modeling
Volume Number	18
Issue Number	5
e-ISSN	09485023
Language	English
Publisher	Springer-Verlag
Publisher Date	2011-08-25
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Bcl-2 Loop modeling MD simulations Apoptosis Flexible loop domain Essential dynamics Health Informatics Life Sciences Computer Application in Life Sciences Molecular Medicine Biomedicine general Computer Applications in Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Physical and Theoretical Chemistry Computational Theory and Mathematics Catalysis Inorganic Chemistry Computer Science Applications

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