Physical nature of intermolecular interactions inside Sir2 homolog active site: molecular dynamics and ab initio study.

Przemysław Czeleń,Żaneta Czyżnikowska

doi:10.1007/s00894-016-2992-2

Przemysław Czeleń, Żaneta Czyżnikowska

Open Access

https://doi.org/10.1007/s00894-016-2992-2

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Abstract

In the present study, we analyze the interactions of NAD+-dependent deacetylase (Sir2 homolog yeast Hst2) with carba-nicotinamide-adenine-dinucleotide (ADP-HPD). For the Sir2 homolog, a yeast Hst2 docking procedure was applied. The structure of the protein–ADP-HPD complex obtained during the docking procedure was used as a starting point for molecular dynamics simulation. The intermolecular interaction energy partitioning was performed for protein–ADP-HPD complex resulting from molecular dynamics simulation. The analysis was performed for ADP-HPD and 15 amino acids forming a deacetylase binding pocket. Although the results indicate that the first-order electrostatic interaction energy is substantial, the presence of multiple hydrogen bonds in investigated complexes can lead to significant value of induction component.

Highlights

Weak noncovalent interactions involving molecules of biological importance have been identified to play an important roleDue to their biochemical properties Sir2 proteins are involved in various biological processes such as DNA metabolism, regulation, and repair of double-stranded breaks [2, 3]
The trajectory obtained during 40 ns of equilibrated molecular dynamic simulation allowed evaluating the stability of the considered interactions
Bonds created by ADP-HPD with ILE117 and ASP118 are stable over all simulation times, in the case of bonds created by first amino acid interactions of medium and weak binding power dominate, while ASP118 creates mainly strong hydrogen bonds

Summary

Introduction

Weak noncovalent interactions involving molecules of biological importance have been identified to play an important role. Due to their biochemical properties Sir (silent information regulator 2) proteins are involved in various biological processes such as DNA metabolism, regulation, and repair of double-stranded breaks [2, 3]. This group of proteins can be involved in transcriptional silencing, apoptosis and chromosome stability. The docking procedure and molecular dynamics simulations were performed in order to gain an insight into the structural and energetical basis

Methods

Results

Conclusion