Dataset Information

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

ABSTRACT: 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 ?s 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 ?2 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 ?2 helix, and the other has the looser ?-barrel with disjointing ?D-?E strands. Our results provide atomic-level descriptions of the binding-relevant intermediate states and could improve our understanding of the binding mechanism.

SUBMITTER: Guo Y

PROVIDER: S-EPMC6678811 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Guo Yue Y Duan Mojie M Yang Minghui M

International journal of molecular sciences 20190715 14

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 properti ...[more]

PMID: 31311155

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Dataset Information

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

Publications

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

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