Replica exchange molecular dynamics simulations reveal the structural and molecular properties of levan-type fructo-oligosaccharides of various chain lengths

Abstract

BackgroundLevan and levan-type fructo-oligosaccharides (LFOs) have various potential applications in pharmaceutical and food industries due to their beneficial properties such as their low intrinsic viscosity and high water solubility. Previous studies showed that they exhibited prebiotic effects, anti-inflammatory and anti-tumor activities against Sarcoma-180 tumor cells of human. Despite their various potential applications, the structural and molecular properties of LFOs of various chain lengths are not well understood.ResultsWe employed the replica-exchange molecular dynamics simulations method (REMD) in AMBER14 to elucidate structural and molecular properties of LFOs with chain lengths of 5 (LFO5), 10 (LFO10) and 15 (LFO15) residues in two models of generalized Born implicit solvent (GBHCT and GBOBC1). For LFO10 and LFO15, four distinct conformations (helix-like, partial helix, zig-zag and random structures) were characterized by their upper-middle and lower-middle torsions. For LFO5, two distinct conformations (partial helix and random structures) were characterized by their middle torsion and molecular angle of residues 1, 3 and 5. To determine hydrogen bonds important for the formation of helix-like structures of LFO10 and LFO15, occurrence frequencies of hydrogen bonds were analyzed, and the O6(i)--H3O(i+1) hydrogen bond was found with the highest frequency, suggesting its importance in helix formation. Among three dihedral angles between two fructosyl units [ϕ (O5’-C2’-O6-C6), ψ (C2’-O6-C6-C5) and ω (O6-C6-C5-C4)], dihedral angle distributions showed that ω was the most flexible dihedral angle and probably responsible for conformational differences of LFOs.ConclusionsOur study provides important insights into the structural and molecular properties of LFOs, which tend to form helical structures as the chain length increases from 5 to 15 residues. This information could be beneficial for the selection of LFOs with appropriate lengths and properties for pharmaceutical and biological applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1182-7) contains supplementary material, which is available to authorized users.

Unraveling the structural and molecular properties of 34-residue levans with various branching degrees by replica exchange molecular dynamics simulations

“…Helix-like structures adopted conformations of left-handed 3-fold helices, where each helical turn consisted of three fructosyl residues ( Fig 1c ). These results are consistent with previous findings that levan tends to form helix-like structures as its chain length increases from 5 to 15 residues [ 23 ]. In nature, kinks are also observed in DNA structures [ 30 ], long α-helical membrane proteins and soluble proteins (≥ 20 residues) [ 31 ].…”

“…For all systems simulated in the GB HCT or GB OBC1 model, the O1 (i) —H3O (i) and O5 (i) —H1O (i) hydrogen bonds had the second and third highest frequencies, respectively; O1 (i) —H3O (i) and O5 (i) —H1O (i) hydrogen bonds are hydrogen bonds within the same residue ( Table 2 , S3 Table and Fig 4a ). The trends for O6 (i) —H3O (i+1), O1 (i) —H3O (i) and O5 (i) —H1O (i) hydrogen bonds of these systems are similar to those found in the helix-like structures of LFO 10 and LFO 15 [ 23 ] probably because they all form helix-like structures, and these hydrogen bonds are likely to be important for helix formation. However, the occurrence frequencies of O6 (i) —H3O (i+1) hydrogen bond per structure of L 34B0 , L 34B1 , L 34B3 and L 34B5 are lower than those of the helix-like structures of LFO 10 and LFO 15 .…”

“…These results show that ω is probably more flexible than ψ and ϕ because it has more possibilities in rotating and changing levan conformations. The trends of the occurrence frequencies of ω, ψ and ϕ of the main chains of these systems are similar to those of levan oligosaccharides with the chain lengths of 5, 10 and 15 residues [ 23 ].…”

“…Moreover, REMD was employed to investigate the conformational properties of a linear N-glycan [ 21 ], and a branched N-glycan found in the HIV envelop protein gp120 [ 21 , 22 ]. Recently, we used REMD to elucidate the structural and molecular properties of levan oligosaccharides (LFOs) with chain lengths of 5, 10 and 15 residues in two models of generalized Born implicit solvent (GB HCT and GB OBC1 ) [ 23 ]. We found that LFOs tended to form helix-like structures as chain length increased from 5 to 15 residues [ 23 ].…”

“…Recently, we used REMD to elucidate the structural and molecular properties of levan oligosaccharides (LFOs) with chain lengths of 5, 10 and 15 residues in two models of generalized Born implicit solvent (GB HCT and GB OBC1 ) [ 23 ]. We found that LFOs tended to form helix-like structures as chain length increased from 5 to 15 residues [ 23 ]. However, to our knowledge, REMD has not been used to explore the conformational spaces of levan with various branching degrees in solution or to elucidate their properties.…”