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A Molecular Dynamics Study of Interaction between Kinesin Light Chain and Amyloid Precursor Protein
Author(s) -
Taylor Cooper,
Shah Soleil,
Miller Bill,
Parish Carol
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.564.9
Subject(s) - ternary complex , chemistry , amyloid precursor protein , protein folding , protein structure , biochemistry , medicine , alzheimer's disease , disease , pathology , enzyme
The misregulation of the cargo binding domain of kinesin‐1 light chain (KLC) has been linked to various neurodegenerative diseases, most notably Alzheimer's, as KLC may play a role in amyloid precursor protein (APP) transport and subsequent degradation. Recent literature suggests a third protein, C‐Jun‐amino‐terminal kinase‐interacting protein 1 (JIP1), acts as a mediator protein for binding of KLC to APP. Computational molecular dynamics (MD) was conducted on this ternary complex, as well as the JIP1:KLC complex, using the Amber MD package to understand the atomistic interactions between the structures. Schrodinger's Glide was used to dock the structure of JIP1 (extracted from PDB 2H96) to KLC to form the binary complex, while the online Patchdock server was used to dock APP to the JIP1:KLC complex to form the ternary state. Within simulations of various JIP1:KLC complexes, the JIP1 protein would orient itself in nearly the same location relative to KLC regardless of the initial starting conformation used for MD. The simulations were also used to help elucidate a low energy conformation of the bound complex, since this conformation has not been resolved experimentally. Preliminary binding free energy calculations suggest that the ternary complex is more stable than the binary complex (APP:KLC).