Molecular dynamics simulation of tau peptides for the investigation of conformational changes induced by specific phosphorylation patterns
MetadataShow full item record
The Tau protein plays an important role due to its biomolecular interactions in neurodegenerative diseases. The lack of stable structure and various posttranslational modifications such as phosphorylation at various sites in the Tau protein pose a challenge for many experimental methods that are traditionally used to study protein folding and aggregation. Atomistic molecular dynamics (MD) simulations can help around deciphering relationship between phosphorylation and various intermediate and stable conformations of the Tau protein which occur on longer timescales. This chapter outlines protocols for the preparation, execution, and analysis of all-atom MD simulations of a 21-amino acid-long phosphorylated Tau peptide with the aim of generating biologically relevant structural and dynamic information. The simulations are done in explicit solvent and starting from nearly extended configurations of the peptide. The scaled MD method implemented in AMBER14 was chosen to achieve enhanced conformational sampling in addition to a conventional MD approach, thereby allowing the characterization of folding for such an intrinsically disordered peptide at 293 K. Emphasis is placed on the analysis of the simulation trajectories to establish correlations with NMR data (i.e., chemical shifts and NOEs). Finally, in-depth discussions are provided for commonly encountered problems.
Showing items related by title, author, creator and subject.
Molecular dynamics simulation of the phosphorylation-induced conformational changes of a tau peptide fragmentLyons, Albert; Gandhi, Neha; Mancera, Ricardo (2014)Aggregation of the microtubule associated protein tau (MAPT) within neurons of the brain is the leading cause of tauopathies such as Alzheimer's disease. MAPT is a phospho-protein that is selectively phosphorylated by a ...
Kang, J.; Chong, S.; Ooi, V.; Vali, S.; Kumar, A.; Kapoor, S.; Abbasi, T.; Hirpara, J.; Loh, T.; Goh, B.; Pervaiz, Shazib (2015)We recently reported a novel interaction between Bcl-2 and Rac1 and linked that to the ability of Bcl-2 to induce a pro-oxidant state in cancer cells. To gain further insight into the functional relevance of this interaction, ...
Free energy of binding of coiled-coil complexes with different electrostatic environments: the influence of force field polarisation and cappingZhuo, Z.; Guo, L.; Mancera, Ricardo (2014)Coiled-coils are well known protein–protein interaction motifs, with the leucine zipper region of activator protein-1 (AP-1) consisting of the c-Jun and c-Fos proteins being a typical example. Molecular dynamics (MD) ...