Molecular dynamics study of protein-oligosaccharide interaction mechanisms in chitinases

Nana Munck, Kirsi Tappura, Hannu Maaheimo, Harry Boer, Maija Mattinen, Anu Koivula

Research output: Contribution to journalOther journal contributionScientific

Abstract

Protein-carbohydrate interactions, essential in many biomolecular recognition events, are investigated by extended molecular dynamic (MD) simulations with explicit water. The aim is to obtain atomic level information on the binding and to gain a deeper understanding of the factors determining the interactions between an oligosaccharide and a protein. The study concentrates on 42kDa chitinase from Trichoderma harzianum containing an extended binding site providing a number of strong and specific interactions with up to 6-7 sugar units. Since these interactions come from a limited number of loops, the substrate binding specificity can be altered by locally directed saturation mutagenesis. While experimentally determined three-dimensional structures were not available for the enzyme of interest, structural models were constructed based on the known structures of homologues. Experimentally determined sugar-protein complex structures of related chitinases were used in the initial simulations to evaluate the suitability of the force field parameters and simulation procedures. Classical MD (Gromacs) with a conventional force field and with a soft-core potential [1] is used to explore the conformational space of the chitinase loops and to study the functional behavior of the N-acetylglucosamine oligosaccharides and their derivates. Trajectories obtained from the simulations are used in analyzing the binding, especially the hydrogen bonding and hydrophobic interactions occurring via N/O-acetyl or O-methyl groups. When available, results from nuclear magnetic resonance spectroscopy are used to support and direct the computational studies and mutagenesis work. [1] Tappura et al.. J. Comput. Chem. 21 (2000) 388 and Proteins 44 (2001) 167.
Original languageEnglish
Pages (from-to)250
Number of pages1
JournalEuropean Biophysics Journal
Volume34
Issue number3
DOIs
Publication statusPublished - 2003
MoE publication typeB1 Article in a scientific magazine
Event4th Eur. Biophysics Congr. Alicante, Spain, 5 - 9 July 2003 -
Duration: 1 Jan 2003 → …

Fingerprint

Chitinases
Molecular Dynamics Simulation
Oligosaccharides
Mutagenesis
Proteins
Trichoderma
Acetylglucosamine
Structural Models
Hydrogen Bonding
Substrate Specificity
Hydrophobic and Hydrophilic Interactions
Magnetic Resonance Spectroscopy
Binding Sites
Carbohydrates
Water
Enzymes

Cite this

@article{58e740084e214d8db219e2e5b514cdd0,
title = "Molecular dynamics study of protein-oligosaccharide interaction mechanisms in chitinases",
abstract = "Protein-carbohydrate interactions, essential in many biomolecular recognition events, are investigated by extended molecular dynamic (MD) simulations with explicit water. The aim is to obtain atomic level information on the binding and to gain a deeper understanding of the factors determining the interactions between an oligosaccharide and a protein. The study concentrates on 42kDa chitinase from Trichoderma harzianum containing an extended binding site providing a number of strong and specific interactions with up to 6-7 sugar units. Since these interactions come from a limited number of loops, the substrate binding specificity can be altered by locally directed saturation mutagenesis. While experimentally determined three-dimensional structures were not available for the enzyme of interest, structural models were constructed based on the known structures of homologues. Experimentally determined sugar-protein complex structures of related chitinases were used in the initial simulations to evaluate the suitability of the force field parameters and simulation procedures. Classical MD (Gromacs) with a conventional force field and with a soft-core potential [1] is used to explore the conformational space of the chitinase loops and to study the functional behavior of the N-acetylglucosamine oligosaccharides and their derivates. Trajectories obtained from the simulations are used in analyzing the binding, especially the hydrogen bonding and hydrophobic interactions occurring via N/O-acetyl or O-methyl groups. When available, results from nuclear magnetic resonance spectroscopy are used to support and direct the computational studies and mutagenesis work. [1] Tappura et al.. J. Comput. Chem. 21 (2000) 388 and Proteins 44 (2001) 167.",
author = "Nana Munck and Kirsi Tappura and Hannu Maaheimo and Harry Boer and Maija Mattinen and Anu Koivula",
note = "Poster abstract",
year = "2003",
doi = "10.1007/s00249-003-0324-9",
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pages = "250",
journal = "European Biophysics Journal",
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Molecular dynamics study of protein-oligosaccharide interaction mechanisms in chitinases. / Munck, Nana; Tappura, Kirsi; Maaheimo, Hannu; Boer, Harry; Mattinen, Maija; Koivula, Anu.

In: European Biophysics Journal, Vol. 34, No. 3, 2003, p. 250.

Research output: Contribution to journalOther journal contributionScientific

TY - JOUR

T1 - Molecular dynamics study of protein-oligosaccharide interaction mechanisms in chitinases

AU - Munck, Nana

AU - Tappura, Kirsi

AU - Maaheimo, Hannu

AU - Boer, Harry

AU - Mattinen, Maija

AU - Koivula, Anu

N1 - Poster abstract

PY - 2003

Y1 - 2003

N2 - Protein-carbohydrate interactions, essential in many biomolecular recognition events, are investigated by extended molecular dynamic (MD) simulations with explicit water. The aim is to obtain atomic level information on the binding and to gain a deeper understanding of the factors determining the interactions between an oligosaccharide and a protein. The study concentrates on 42kDa chitinase from Trichoderma harzianum containing an extended binding site providing a number of strong and specific interactions with up to 6-7 sugar units. Since these interactions come from a limited number of loops, the substrate binding specificity can be altered by locally directed saturation mutagenesis. While experimentally determined three-dimensional structures were not available for the enzyme of interest, structural models were constructed based on the known structures of homologues. Experimentally determined sugar-protein complex structures of related chitinases were used in the initial simulations to evaluate the suitability of the force field parameters and simulation procedures. Classical MD (Gromacs) with a conventional force field and with a soft-core potential [1] is used to explore the conformational space of the chitinase loops and to study the functional behavior of the N-acetylglucosamine oligosaccharides and their derivates. Trajectories obtained from the simulations are used in analyzing the binding, especially the hydrogen bonding and hydrophobic interactions occurring via N/O-acetyl or O-methyl groups. When available, results from nuclear magnetic resonance spectroscopy are used to support and direct the computational studies and mutagenesis work. [1] Tappura et al.. J. Comput. Chem. 21 (2000) 388 and Proteins 44 (2001) 167.

AB - Protein-carbohydrate interactions, essential in many biomolecular recognition events, are investigated by extended molecular dynamic (MD) simulations with explicit water. The aim is to obtain atomic level information on the binding and to gain a deeper understanding of the factors determining the interactions between an oligosaccharide and a protein. The study concentrates on 42kDa chitinase from Trichoderma harzianum containing an extended binding site providing a number of strong and specific interactions with up to 6-7 sugar units. Since these interactions come from a limited number of loops, the substrate binding specificity can be altered by locally directed saturation mutagenesis. While experimentally determined three-dimensional structures were not available for the enzyme of interest, structural models were constructed based on the known structures of homologues. Experimentally determined sugar-protein complex structures of related chitinases were used in the initial simulations to evaluate the suitability of the force field parameters and simulation procedures. Classical MD (Gromacs) with a conventional force field and with a soft-core potential [1] is used to explore the conformational space of the chitinase loops and to study the functional behavior of the N-acetylglucosamine oligosaccharides and their derivates. Trajectories obtained from the simulations are used in analyzing the binding, especially the hydrogen bonding and hydrophobic interactions occurring via N/O-acetyl or O-methyl groups. When available, results from nuclear magnetic resonance spectroscopy are used to support and direct the computational studies and mutagenesis work. [1] Tappura et al.. J. Comput. Chem. 21 (2000) 388 and Proteins 44 (2001) 167.

U2 - 10.1007/s00249-003-0324-9

DO - 10.1007/s00249-003-0324-9

M3 - Other journal contribution

VL - 34

SP - 250

JO - European Biophysics Journal

JF - European Biophysics Journal

SN - 0175-7571

IS - 3

ER -