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.

• Klíčová slova
• adaptive biasing force simulations, biasing potential replica-exchange simulation, conformational sampling, molecular dynamics simulation, saccharides,
• MeSH
• antigeny krevních skupin chemie   genetika   MeSH
• disacharidy chemie   genetika   MeSH
• konformace sacharidů MeSH
• lidé MeSH
• sekvenční analýza * MeSH
• simulace molekulární dynamiky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny krevních skupin MeSH
• disacharidy MeSH

The opportunistic pathogen Burkholderia cenocepacia expresses several soluble lectins, among them BC2L-C. This lectin exhibits two domains: a C-terminal domain with high sequence similarity to the recently described calcium-dependent mannose-binding lectin BC2L-A, and an N-terminal domain of 156 amino acids without similarity to any known protein. The recombinant N-terminal BC2L-C domain is a new lectin with specificity for fucosylated human histo-blood group epitopes H-type 1, Lewis b, and Lewis Y, as determined by glycan array and isothermal titration calorimetry. Methylselenofucoside was used as ligand to solve the crystal structure of the N-terminal BC2L-C domain. Additional molecular modeling studies rationalized the preference for Lewis epitopes. The structure reveals a trimeric jellyroll arrangement with striking similarity to TNF-like proteins, and to BclA, the spore protein from Bacillus anthracis which may play an important role in bioadhesion of anthrax spores in human lungs.

• MeSH
• antigeny krevních skupin chemie   imunologie   metabolismus   MeSH
• bakteriální proteiny chemie   metabolismus   MeSH
• Burkholderia chemie   metabolismus   MeSH
• epitopy chemie   imunologie   metabolismus   MeSH
• fukosa chemie   metabolismus   MeSH
• kvarterní struktura proteinů MeSH
• lektiny chemie   metabolismus   MeSH
• lidé MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny krevních skupin MeSH
• bakteriální proteiny MeSH
• epitopy MeSH
• fukosa MeSH
• lektiny MeSH