Stochastic conformational search on the Lewis X (Le<sup>x</sup>) trisaccharide and three Le<sup>x</sup> analogues
Bibliographic record
Abstract
Biased stochastic conformational searches using the MMFF94 force field and the Born continuum solvation model were applied to the molecular modeling of the Lewis X (Lex) trisaccharide (β-D-Gal-(1,4)-[α-L-Fuc-(1,3)]-β-D-GlcNAc-OH) and three Lex analogues, in which each of the three sugar units was replaced by another sugar residue, i.e., N-acetyl-glucosamine by glucose, galactose by glucose, and fucose by rhamnose. The stochastic search accurately identified a lowest energy conformation of the Lex determinant that corresponds to the reported conformations of Lex deduced experimentally in the solid state by X-ray crystallography and in solution by NMR measurements. In this conformation stacking exists between the galactosyl and fucosyl residues. Five new local minima for the Lex trisaccharide were found within 3 kcal mol1 of the global minimum using the stochastic search and metric scaling. Modeling studies of the analogues showed that the stacking observed in the Lex trisaccharide was maintained when either galactosyl or N-acetylglucosamine were replaced by glucosyl residues. In contrast, substitution of the fucose residue by rhamnose led to two conformers in which stacking of the galactose and rhamnose residues was no longer maintained. These results indicate that the substitution of the non-reducing end galactosyl or N-acetyl-glucosaminyl residues by a glucose unit in the dimeric Lewis X (dimLex) tumour associated antigen could help in the development of a vaccine that cross-reacts with dimLex but no longer displays Lex associated three-dimensional epitopes also presented by non-cancerous cells. In contrast, an analogue in which the fucosyl residue is replaced by rhamnose does not constitute a good vaccine candidate, since our results indicate that this substitution will induce an important conformational change that is likely to abolish cross-reactivity with the natural dimLex tumor associated antigen.Key words: molecular modeling, stochastic, conformational analysis, Lewis X, oligosaccharide.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".