BGPT: Which amino acids could form strong hydrogen bonds with other amino acids within the same polypeptide?

Explore by Goal

Quick Analysis Plan Copied

Ionizable and polar side chains—Asp, Glu, Lys, Arg, His, Asn, Gln, Ser, Thr, Tyr, Trp—form the strongest intra-polypeptide hydrogen bonds because they carry donor/acceptor groups; structural surveys show 69% of intramolecular ionizable-side-chain interactions are hydrogen bonds, often to main-chain NH/CO groups, with strong helix-termini and burial biases.

Long Analysis Plan

Direct answer from structural evidence

A 44-structure, 6,616-residue PDB survey (H-bond cutoff ≤3.5 Å donor–acceptor) found that ionizable side chains (Asp, Glu, Lys, Arg, His) overwhelmingly interact via hydrogen bonds rather than pure salt bridges: 69% of interactions were H-bonds to uncharged groups, and 78% of H-bonds between ionizable side chains and main-chain polar groups involved ≥1 buried atom . Physicochemical reasoning (BGPT inference, not directly reported): strong intra-chain H-bond donors/acceptors are Asp/Glu (COO⁻), Lys/Arg/His (charged or neutral amines/imidazole), Asn/Gln, Ser/Thr/Tyr (OH), Trp (indole NH), plus backbone NH/CO of every residue. Thermodynamic support: side-chain interaction strength is context-dependent—aromatic side-chain contacts (Trp, Phe) were strongest in aqueous chromatographic tests, while histidine H-bonding/salt-bridge behavior is pH-dependent (imidazolium form engages more strongly at higher pH) .

Charged side chains (Arg −15.84, Lys +6.68 kJ/mol) behave distinctly from neutral polar ones (Asn 21.64, Gln 22.50 kJ/mol) in ionic solution, reflecting their different ionization and H-bonding capacity .

Bioinformatics analysis plan

1. Data: download ≥500 non-redundant PDB chains (resolution ≤2.0 Å); add hydrogens; assign DSSP secondary structure and Lee-Richards SASA (burial ≤1 Å² criterion).
2. H-bond detection: per Baker-Hubbard criteria — donor–acceptor distance ≤3.5 Å plus D-H···A angle cutoffs; classify pair type (sidechain–sidechain, sidechain–mainchain, salt-bridged H-bond). Exclude waters, ions, cofactors.
3. Quantify strength: count frequencies and geometric quality (shorter distance, linear angle ⇒ stronger); weight by burial; report a residue-pair 20×20 frequency matrix; compute enrichment vs. sequence-random expectation (binomial test, FDR-corrected).
4. Validation: cross-check against NMR ensembles for dynamics; confirm helix-termini and β-strand biases reproduce the reported patterns.

Confidence: high for the residue list (backed by a strong structural survey); moderate for strength ranking, since geometric cutoffs, static structures, 44-structure sample size, and protonation-state assumptions limit precision. What would change the answer: a much larger survey or MD-derived H-bond lifetimes showing different pair-type frequencies, or different burial criteria.

Feedback:

Updated: September 12, 2026

Top Data Sources Export MCP

1. This study investigates the dissolution enthalpies of various natural amino acids in aqueous potassium chloride solutions, revealing how the side chains of these amino acids influence their interparticle interactions with the dissociated ions. [2018]

8QualityResults Limitations Context Blindspots Methods Sample Conflict Data

↗ Paper Review ↗ Full Paper

2. This study investigates the factors influencing the stability of alpha helices in proteins, focusing on the contributions of amino acid side chains and their interactions, while proposing methods for predicting helix content based on these interactions. [1998]

8QualityResults Limitations Context Blindspots Methods Sample

↗ Paper Review ↗ Full Paper

3. MSP-based chromatographic retention provides lower-bound estimates of relative free energies for amino-acid side-chain interactions (AAG_ij) in aqueous solution, enabling assessment of early protein-folding contacts and indicating aromatic interactions are particularly favored over aliphatic ones. [1992]

6QualityResults Limitations Context Blindspots Methods Sample Data

↗ Paper Review ↗ Full Paper

4. This study investigates the covalent interactions between amino acid side chains and oxidation products of caffeoylquinic acid, revealing that lysine, tyrosine, histidine, and tryptophan can react with CQA dimers, which may influence protein modification in food products. [2008]

8QualityResults Limitations Context Blindspots Methods Sample Data

↗ Paper Review ↗ Full Paper

5. This study employs DFT calculations to analyze the interaction energies of amino acid side chains with various transition metal ions, revealing insights into metal ion selectivity and coordination geometries relevant to bioinorganic chemistry. [2000]

8QualityResults Limitations Context Blindspots Methods Sample

↗ Paper Review ↗ Full Paper

Key Insight

Backbone NH/CO groups are the universal H-bonding partner: even charged side chains mostly H-bond to the main chain (78% involving buried atoms), meaning 'strong' intra-chain H-bonds depend less on which residues than on where they sit—helix N-caps favor Asp/Glu, C-caps favor Lys/Arg.

Keep Exploring

How do hydrogen-bond lifetimes from molecular dynamics compare with static PDB frequency counts as predictors of protein thermal stability for specific residue pairs?

Which specific residue-pair hydrogen bonds (e.g., Asp–Tyr vs Lys–Asp) most stabilize beta-sheet edges against aggregation in human proteins?

Analysis Wizard

Scanning high-resolution PDB structures to count intramolecular hydrogen bonds between amino acid side chains, building a 20×20 residue-pair strength matrix that reveals which residues form the strongest intra-polypeptide H-bonds.

Hypothesis Graveyard

'Only oppositely charged residues form strong intra-chain bonds' — falsified: 69% of ionizable-side-chain interactions are H-bonds to uncharged groups, not pure salt bridges.

'Aromatic side chains cannot H-bond' — partially falsified: Trp indole NH is a donor, though aromatic–aromatic contacts measured chromatographically are dominated by dispersion, not H-bonding.

Potential Experiments

Scan a 100-residue designed helix-turn-helix peptide swapping each i,i+4 pair among 20×20 combinations, measure Tm by CD; a complete H-bond-pair strength map would directly test whether geometric H-bond quality predicts stability better than frequency counts.

Run 100-ns explicit-solvent MD on 20 high-resolution PDB chains and compute H-bond occupancy × lifetime per pair type; compare the MD strength ranking against the static 44-structure survey frequencies to quantify how much dynamics changes the answer.

Science Art

Science Movie

Make a narrated HD Science movie for this answer ($32 per minute)

Discussion

BGPT Bias

I favor large structural surveys and geometric cutoffs, which may underweight dynamic solvent-mediated H-bonds and entropic contributions that MD or calorimetry would reveal.

Stay current without chasing every paper.

Know what changed, what holds up, and what remains uncertain. Every Friday. No ads.

Create Cited Tables

Build tables from exact reported results, each linked to its experiment and source paper.Know what the science actually supports before you trust the answer.

Explore by Goal

Quick Analysis Plan Copied

Long Analysis Plan

Direct answer from structural evidence

Bioinformatics analysis plan

Top Data Sources ExportMCP

1. This study investigates the dissolution enthalpies of various natural amino acids in aqueous potassium chloride solutions, revealing how the side chains of these amino acids influence their interparticle interactions with the dissociated ions. [2018]

2. This study investigates the factors influencing the stability of alpha helices in proteins, focusing on the contributions of amino acid side chains and their interactions, while proposing methods for predicting helix content based on these interactions. [1998]

4. This study investigates the covalent interactions between amino acid side chains and oxidation products of caffeoylquinic acid, revealing that lysine, tyrosine, histidine, and tryptophan can react with CQA dimers, which may influence protein modification in food products. [2008]

5. This study employs DFT calculations to analyze the interaction energies of amino acid side chains with various transition metal ions, revealing insights into metal ion selectivity and coordination geometries relevant to bioinorganic chemistry. [2000]

6. This paper discusses the weak interactions and related functions of side chain groups in metal-amino acid chemistry, highlighting their biological relevance and implications in complex formation. [2002]

8. This study investigates the hydrogen bonding interactions between amino acid side chains and nucleic acid bases, reporting association constants for various compounds in non-polar solvents. [1977]

9. This study develops and validates new 12-6 Lennard-Jones parameters for the interaction of silver(I) ions with amino acid side chains, demonstrating their applicability in molecular dynamics simulations to better understand silver(I) binding in biological systems. [2024]

10. This study investigates the limiting essential amino acids in soybean meal for growing chickens and examines how different heat treatments affect the availability of these amino acids. [1968]

11. Automated identification and classification of beta-bulges in protein beta-sheets across 170 proteins reveals bulges are common, predominantly antiparallel, and can be categorized into distinct types with characteristic hydrogen-bond patterns and amino-acid preferences. [1993]

12. This study demonstrates the successful use of the DNA triplet GCA as a chiral selector for the discrimination of amino acids, achieving significant chiral selectivity through the use of amino acids as co-selectors. [2007]

Ask a Follow-Up

Key Insight

Backbone NH/CO groups are the universal H-bonding partner: even charged side chains mostly H-bond to the main chain (78% involving buried atoms), meaning 'strong' intra-chain H-bonds depend less on which residues than on where they sit—helix N-caps favor Asp/Glu, C-caps favor Lys/Arg.

Keep Exploring

How do hydrogen-bond lifetimes from molecular dynamics compare with static PDB frequency counts as predictors of protein thermal stability for specific residue pairs?

Which specific residue-pair hydrogen bonds (e.g., Asp–Tyr vs Lys–Asp) most stabilize beta-sheet edges against aggregation in human proteins?

Analysis Wizard

Scanning high-resolution PDB structures to count intramolecular hydrogen bonds between amino acid side chains, building a 20×20 residue-pair strength matrix that reveals which residues form the strongest intra-polypeptide H-bonds.

Hypothesis Graveyard

'Only oppositely charged residues form strong intra-chain bonds' — falsified: 69% of ionizable-side-chain interactions are H-bonds to uncharged groups, not pure salt bridges.

'Aromatic side chains cannot H-bond' — partially falsified: Trp indole NH is a donor, though aromatic–aromatic contacts measured chromatographically are dominated by dispersion, not H-bonding.

Potential Experiments

Scan a 100-residue designed helix-turn-helix peptide swapping each i,i+4 pair among 20×20 combinations, measure Tm by CD; a complete H-bond-pair strength map would directly test whether geometric H-bond quality predicts stability better than frequency counts.

Run 100-ns explicit-solvent MD on 20 high-resolution PDB chains and compute H-bond occupancy × lifetime per pair type; compare the MD strength ranking against the static 44-structure survey frequencies to quantify how much dynamics changes the answer.

Science Art

Science Movie

Make a narrated HD Science movie for this answer ($32 per minute)

Discussion

BGPT Bias

I favor large structural surveys and geometric cutoffs, which may underweight dynamic solvent-mediated H-bonds and entropic contributions that MD or calorimetry would reveal.

Stay current without chasing every paper.

My BGPT

Trending

Top Data Sources Export MCP