To probe the binding pathway of a selective compound (D089-0563) to c-MYC Pu24 G-quadruplex using free ligand binding simulations and Markov state model analysis

2020 ◽  
Vol 22 (39) ◽  
pp. 22567-22583
Author(s):  
Brian Chen ◽  
Griffin Fountain ◽  
Holli-Joi Sullivan ◽  
Nicholas Paradis ◽  
Chun Wu
Keyword(s):  
Ligand Binding ◽  
Promoter Region ◽  
Free Ligand ◽  
State Model ◽  
Binding Mechanism ◽  
Myc Oncogene ◽  
Markov State Model ◽  
Markov State ◽  
Anti Cancer ◽  
G Quadruplex

D089-0563 is a highly promising anti-cancer compound that selectively binds the transcription-silencing G-quadruplex element (Pu27) at the promoter region of the human c-MYC oncogene; however, its binding mechanism remains elusive.

scholarly journals Fast-Folding Pathways of the Thrombin-Binding Aptamer G-Quadruplex Revealed by a Markov State Model

2018 ◽  
Vol 114 (7) ◽  
pp. 1529-1538 ◽  
Author(s):  
Yunqiang Bian ◽  
Feng Song ◽  
Zanxia Cao ◽  
Liling Zhao ◽  
Jiafeng Yu ◽  
...  
Keyword(s):  
State Model ◽  
Markov State Model ◽  
Markov State ◽  
G Quadruplex ◽  
Folding Pathways

scholarly journals Quantitatively Characterizing the Ligand Binding Mechanisms of Choline Binding Protein Using Markov State Model Analysis

2014 ◽  
Vol 10 (8) ◽  
pp. e1003767 ◽  
Author(s):  
Shuo Gu ◽  
Daniel-Adriano Silva ◽  
Luming Meng ◽  
Alexander Yue ◽  
Xuhui Huang
Keyword(s):  
Ligand Binding ◽  
Binding Protein ◽  
Model Analysis ◽  
State Model ◽  
Markov State Model ◽  
Markov State ◽  
Binding Mechanisms

scholarly journals The Observation of Ligand-Binding-Relevant Open States of Fatty Acid Binding Protein by Molecular Dynamics Simulations and a Markov State Model

2019 ◽  
Vol 20 (14) ◽  
pp. 3476 ◽  
Author(s):  
Yue Guo ◽  
Mojie Duan ◽  
Minghui Yang
Keyword(s):  
Fatty Acid ◽  
Ligand Binding ◽  
Md Simulations ◽  
Binding Mechanism ◽  
Fatty Acid Binding ◽  
Markov State Model ◽  
Markov State ◽  
Intermediate States ◽  
Partially Unfolded ◽  
Open States

As a member of the fatty acids transporter family, the heart fatty acid binding proteins (HFABPs) are responsible for many important biological activities. The binding mechanism of fatty acid with FABP is critical to the understanding of FABP functions. The uncovering of binding-relevant intermediate states and interactions would greatly increase our knowledge of the binding process. In this work, all-atom molecular dynamics (MD) simulations were performed to characterize the structural properties of nativelike intermediate states. Based on multiple 6 μs MD simulations and Markov state model (MSM) analysis, several “open” intermediate states were observed. The transition rates between these states and the native closed state are in good agreement with the experimental measurements, which indicates that these intermediate states are binding relevant. As a common property in the open states, the partially unfolded α2 helix generates a larger portal and provides the driving force to facilitate ligand binding. On the other side, there are two kinds of open states for the ligand-binding HFABP: one has the partially unfolded α2 helix, and the other has the looser β-barrel with disjointing βD-βE strands. Our results provide atomic-level descriptions of the binding-relevant intermediate states and could improve our understanding of the binding mechanism.

scholarly journals A Markov-State Model for the Regulation of the Sarcoplasmic Reticulum Ca2+ ATPase by Phospholamban

2014 ◽  
Vol 106 (2) ◽  
pp. 116a
Author(s):  
Peter M. Kekenes-Huskey ◽  
Andy Edwards ◽  
Johan Hake ◽  
Anouchka Michailova ◽  
James A. McCammon ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
State Model ◽  
Markov State Model ◽  
Markov State
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