Science China Chemistry

, Volume 56, Issue 8, pp 1143–1151 | Cite as

Interaction specific binding hotspots in Endonuclease colicin-immunity protein complex from MD simulations

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Abstract

The binding of Endonuclease colicin 9 (E9) by Immunity protein 9 (Im9) was found to involve some hotspots from helix III of Im9 on protein-protein interface that contribute the dominant binding energy to the complex. In the current work, MD simulations of the WT and three hotspot mutants (D51A, Y54A and Y55A of Im9) of the E9-Im9 complexes were carried out to investigate specific interaction mechanisms of these three hotspot residues. The changes of binding energy between the WT and mutants of the complex were computed by the MM/PBSA method using a polarized force field and were in excellent agreement with experiment values, verifying that these three residues were indeed hotspots of the binding complex. Energy decomposition analysis revealed that binding by D51 to E9 was dominated by electrostatic interaction due to the presence of the carboxyl group of Asp51 which hydrogen bonds to K89. For binding by hotspots Y54 and Y55, van der Waals interaction from the aromatic side chain of tyrosine provided the dominant interaction. For comparison, calculation by using the standard (nonpolarizable) AMBER99SB force field produced binding energy changes from these mutations in opposite direction to the experimental observation. Dynamic hydrogen bond analysis showed that conformations sampled from MD simulation in the standard AMBER force field were distorted from the native state and they disrupted the inter-protein hydrogen bond network of the protein-protein complex. The current work further demonstrated that electrostatic polarization plays a critical role in modulating protein-protein binding.

Keywords

protein-protein interaction binding hotspot mutation Endonuclease Colicin immunity protein MD simulation 
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Copyright information

© Science China Press and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.School of Chemistry and Chemical EngineeringNanjing UniversityNanjingChina
  2. 2.College of EngineeringNanjing Agricultural UniversityNanjingChina
  3. 3.State Key Laboratory of Precision Spectroscopy, Department of PhysicsEast China Normal UniversityShanghaiChina
  4. 4.Department of ChemistryNew York UniversityNew YorkUSA

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