Elucidating the Intermolecular Interactions within a Desolvated Protein−Ligand Complex. An Experimental and Computational Study
Bibliographic record
Abstract
The first detailed study of the intermolecular hydrogens bonds (H-bonds) within a desolvated, noncovalent protein-ligand complex is reported. Using both experimental and computational methods, the intermolecular H-bonds stabilizing protonated and deprotonated ions of a complex composed of a single chain fragment (scFv) of a monoclonal antibody and its native trisaccharide ligand, alphaGal[alphaAbe] alphaMan (1), are characterized. Using the blackbody infrared radiative dissociation-functional group replacement (BIRD/FGR) technique, three H-bond donor-acceptor pairs within the gaseous (scFv + 1)n+ ions are identified and quantified. Additional sites of interaction on the protein and ligand, for which the binding partner could not be elucidated, are also identified. Comparison of the gas-phase interaction maps with the crystal structure suggests that at least two of the specific H-bonds are conserved upon transfer of the complex from solution to the gas phase by electrospray ionization. However, new (nonspecific) interactions can also form in the gas phase. Notably, the nature and strength of the intermolecular interactions can vary significantly with charge state, and striking differences in the structures of the (scFv + 1)n+ and (scFv + 1)n- ions are evident. Intermolecular H-bonds are also identified from molecular dynamics (MD) simulations performed at the +8 and -8 charge states. Agreement is found for a majority of intermolecular interactions predicted for the (scFv + 1)8+ ion by the MD simulation and BIRD/FGR method; the agreement is less favorable in the case of the (scFv + 1)8- ion. However, both the computational and experimental results point to structural differences between the +8 and -8 ions. The computational results also provide insights into the structural changes that accompany the loss of interfacial waters from the complex.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".