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

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 simula- tions of the WT and three hotspot mutants （D51A, Y5...

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Published inScience China. Chemistry Vol. 56; no. 8; pp. 1143 - 1151
Main Authors Yao, XueXia, Ji, ChangGe, Xie, DaiQian, Zhang, John Z. H.
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2013
Springer Nature B.V
Subjects
AMBER力场
Binding energy
Carboxyl group
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
Hydrogen bonds
MD模拟
Proteins
Residues
Simulation
Tyrosine
免疫蛋白
大肠杆菌
核酸内切酶
特异性结合
蛋白质复合物
静电相互作用
MD simulation
binding hotspot
mutation
Endonuclease Colicin
immunity protein
protein-protein interaction
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Summary: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 simula- tions of the WT and three hotspot mutants （D51A, Y54A and Y55A of Im9） of the E9-Im9 complexes were carried out to in- vestigate 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 agree- ment with experiment values, verifying that these three residues were indeed hotspots of the binding complex. Energy decom- position analysis revealed that binding by D51 to E9 was dominated by electrostatic interaction due to the presence of the car- boxyl 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 （non- polarizable） AMBER99SB force field produced binding energy changes from these mutations in opposite direction to the ex- perimental 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.
Bibliography:YAO XueXia, JI ChangGe., XIE DaiQian ＆ ZHANG John Z. H. ISchool of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China 2College of Engineering, Nanjing Agricultural University, Nanjing 210031, China 3State Key Laboratory of Precision Spectroscopy, Department of Physics, East China Normal University, Shanghai 200062, China 4Department of Chemistry, New York University, New York, NY 10003, USA
protein-protein interaction, binding hotspot, mutation, Endonuclease Colicin, immunity protein, MD simulation
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 simula- tions of the WT and three hotspot mutants （D51A, Y54A and Y55A of Im9） of the E9-Im9 complexes were carried out to in- vestigate 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 agree- ment with experiment values, verifying that these three residues were indeed hotspots of the binding complex. Energy decom- position analysis revealed that binding by D51 to E9 was dominated by electrostatic interaction due to the presence of the car- boxyl 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 （non- polarizable） AMBER99SB force field produced binding energy changes from these mutations in opposite direction to the ex- perimental 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.
11-5839/O6
ISSN:1674-7291
1869-1870
DOI:10.1007/s11426-013-4877-x