Molecular Conformations of Di-, Tri-, and Tetra-α-(2→8)-Linked Sialic Acid from NMR Spectroscopy and MD Simulations
| Autor: | Turupcu, Aysegül, Blaukopf, Markus, Kosma, Paul, Oostenbrink, Chris |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Quantitative Biology::Biomolecules
Magnetic Resonance Spectroscopy Molecular Structure Entropy conformational analysis Molecular Conformation Molecular Dynamics Simulation equipment and supplies Article molecular dynamics N-Acetylneuraminic Acid nuclear magnetic resonance sialic acid Thermodynamics human activities |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 1 |
| ISSN: | 1422-0067 |
| Popis: | By using molecular dynamics simulations with an efficient enhanced sampling technique and in combination with nuclear magnetic resonance (NMR) spectroscopy quantitative structural information on &alpha 2,8-linked sialic acids is presented. We used a bottom-up approach to obtain a set of larger ensembles for tetra- and deca-sialic acid from model dimer and trimer systems that are in agreement with the available J-coupling constants and nuclear Overhauser effects. The molecular dynamic (MD) simulations with enhanced sampling are used to validate the force field used in this study for its further use. This empowered us to couple NMR observables in the MD framework via J-coupling and distance restraining simulations to obtain conformations that are supported by experimental data. We used these conformations in thermodynamic integration and one-step perturbation simulations to calculate the free-energy of suggested helical conformations. This study brings most of the available NMR experiments together and supplies information to resolve the conflict on the structures of poly- &alpha 2,8-linked sialic acid. |
| Databáze: | OpenAIRE |
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