Shape: automatic conformation prediction of carbohydrates using a genetic algorithm

BackgroundDetailed experimental three dimensional structures of carbohydrates are often difficult to acquire. Molecular modelling and computational conformation prediction are therefore commonly used tools for three dimensional structure studies. Modelling procedures generally require significant training and computing resources, which is often impractical for most experimental chemists and biologists. Shape has been developed to improve the availability of modelling in this field.ResultsThe Shape software package has been developed for simplicity of use and conformation prediction performance. A trivial user interface coupled to an efficient genetic algorithm conformation search makes it a powerful tool for automated modelling. Carbohydrates up to a few hundred atoms in size can be investigated on common computer hardware. It has been shown to perform well for the prediction of over four hundred bioactive oligosaccharides, as well as compare favourably with previously published studies on carbohydrate conformation prediction.ConclusionThe Shape fully automated conformation prediction can be used by scientists who lack significant modelling training, and performs well on computing hardware such as laptops and desktops. It can also be deployed on computer clusters for increased capacity. The prediction accuracy under the default settings is good, as it agrees well with experimental data and previously published conformation prediction studies. This software is available both as open source and under commercial licenses.

[1]  Osman F. Güner,et al.  Pharmacophore perception, development, and use in drug design , 2000 .

[2]  Norman L. Allinger,et al.  Molecular mechanics. The MM3 force field for hydrocarbons. 3. The van der Waals' potentials and crystal data for aliphatic and aromatic hydrocarbons , 1989 .

[3]  Jimmy Rosen,et al.  Conformation of the branched O-specific polysaccharide of Shigella dysenteriae type 2: molecular mechanics calculations show a compact helical structure exposing an epitope which potentially mimics galabiose. , 2002, Carbohydrate research.

[4]  Egon L. Willighagen,et al.  The Chemistry Development Kit (CDK): An Open-Source Java Library for Chemo-and Bioinformatics , 2003, J. Chem. Inf. Comput. Sci..

[5]  Holger Gohlke,et al.  The Amber biomolecular simulation programs , 2005, J. Comput. Chem..

[6]  Dusan P Djurdjevic,et al.  Ab initio protein fold prediction using evolutionary algorithms: Influence of design and control parameters on performance , 2006, J. Comput. Chem..

[7]  P Willett,et al.  Development and validation of a genetic algorithm for flexible docking. , 1997, Journal of molecular biology.

[8]  David S. Goodsell,et al.  Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function , 1998 .

[9]  Jenn-Huei Lii,et al.  An improved force field (MM4) for saturated hydrocarbons , 1996, Journal of Computational Chemistry.

[10]  David S. Goodsell,et al.  Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function , 1998, J. Comput. Chem..

[11]  Berk Hess,et al.  GROMACS 3.0: a package for molecular simulation and trajectory analysis , 2001 .

[12]  Jimmy Rosen,et al.  The conformations of the O-specific polysaccharides of Shigella dysenteriae type 4 and Escherichia coli O159 studied with molecular mechanics (MM3) filtered systematic search. , 2004, Carbohydrate research.

[13]  N K Kochetkov,et al.  [Molecular structure of the O-specific polysaccharide of Shigella dysenteriae type 2]. , 1984, Doklady Akademii nauk SSSR.

[14]  Serge Pérez,et al.  Prospects for glycoinformatics. , 2005, Current opinion in structural biology.

[15]  Kjeld Rasmussen,et al.  A comparison and chemometric analysis of several molecular mechanics force fields and parameter sets applied to carbohydrates , 1998 .

[16]  Norman L. Allinger,et al.  Molecular mechanics. The MM3 force field for hydrocarbons. 2. Vibrational frequencies and thermodynamics , 1989 .

[17]  Jaroslav Koca,et al.  Conformational analysis and flexibility of carbohydrates using the CICADA approach with MM3 , 1995, J. Comput. Chem..

[18]  Jaroslav Koca,et al.  Conformational analysis of complex oligosaccharides: the CICADA approach to the uromodulin O-glycans. , 2004, Carbohydrate research.

[19]  Norman L. Allinger,et al.  Molecular mechanics. The MM3 force field for hydrocarbons. 1 , 1989 .

[20]  Martin Frank,et al.  Dynamic molecules: molecular dynamics for everyone. An internet-based access to molecular dynamic simulations: basic concepts , 2003, Journal of molecular modeling.

[21]  Jenn-Huei Lii,et al.  An improved force field (MM4) for saturated hydrocarbons , 1996, J. Comput. Chem..

[22]  Jimmy Rosen,et al.  The use of a genetic algorithm search for molecular mechanics (MM3)-based conformational analysis of oligosaccharides. , 2005, Carbohydrate research.

[23]  Jimmy Rosen.  Prediction of 3D structures of oligosaccharides. Methodological development and studies on saccharide antigens of interest for vaccine design , 2005 .

[24]  Jimmy Rosen,et al.  Conformation of the exopolysaccharide of Burkholderia cepacia predicted with molecular mechanics (MM3) using genetic algorithm search. , 2005, Carbohydrate research.