Enhanced conformational sampling of carbohydrates by Hamiltonian replica-exchange simulation

Knowledge of the structure and conformational flexibility of carbohydrates in an aqueous solvent is important to improving our understanding of how carbohydrates function in biological systems. In this study, we extend a variant of the Hamiltonian replica-exchange molecular dynamics (MD) simulation...

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Bibliographic Details
Published inGlycobiology (Oxford) Vol. 24; no. 1; pp. 70 - 84
Main Authors Mishra, Sushil Kumar, Kara, Mahmut, Zacharias, Martin, Koca, Jaroslav
Format Journal Article
LanguageEnglish
Published England 01.01.2014
Subjects
Blood Group Antigens - chemistry
Blood Group Antigens - genetics
Carbohydrate Conformation
Disaccharides - chemistry
Disaccharides - genetics
Humans
Molecular Dynamics Simulation
Sequence Analysis
biasing potential replica-exchange simulation
conformational sampling
saccharides
adaptive biasing force simulations
molecular dynamics simulation
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Summary:Knowledge of the structure and conformational flexibility of carbohydrates in an aqueous solvent is important to improving our understanding of how carbohydrates function in biological systems. In this study, we extend a variant of the Hamiltonian replica-exchange molecular dynamics (MD) simulation to improve the conformational sampling of saccharides in an explicit solvent. During the simulations, a biasing potential along the glycosidic-dihedral linkage between the saccharide monomer units in an oligomer is applied at various levels along the replica runs to enable effective transitions between various conformations. One reference replica runs under the control of the original force field. The method was tested on disaccharide structures and further validated on biologically relevant blood group B, Lewis X and Lewis A trisaccharides. The biasing potential-based replica-exchange molecular dynamics (BP-REMD) method provided a significantly improved sampling of relevant conformational states compared with standard continuous MD simulations, with modest computational costs. Thus, the proposed BP-REMD approach adds a new dimension to existing carbohydrate conformational sampling approaches by enhancing conformational sampling in the presence of solvent molecules explicitly at relatively low computational cost.
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ISSN:0959-6658
1460-2423
DOI:10.1093/glycob/cwt093