Helix Design Studio

About

This application is presented as part of the broader scientific environment connected to SIMBIOS at the Universidade de Santiago de Compostela.

SIMBIOS

Simulating life. Atom by atom.

Universidade de Santiago de Compostela

Helix Design Studio is presented within the broader scientific context of SIMBIOS, a computational biophysics research environment at the University of Santiago de Compostela.

Helix Design Studio

Helix Design Studio is an environment-conditioned sequence-design tool for predefined alpha-helical states. It helps users score sequences, design candidates and families, compare behavior across environments and export ideal helical structures for downstream work.

About the group

SIMBIOS is presented on its website as a computational biophysics research group at the University of Santiago de Compostela. The broader research environment spans molecular simulation, membrane-active systems, biomolecular recognition and data-driven analysis.

Institutional link

For broader institutional and scientific context, publications and group information, visit the official SIMBIOS website.

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Guide and Interpretation

This application scores how well a sequence fits a target alpha-helical state under a chosen environment model. It does not predict full folding from scratch or experimental activity directly.

What the app does

Use Score to evaluate one sequence, Design to search for a low-energy sequence in one environment, Family to generate several diverse candidates, Compare to inspect the same sequence in two environments, and Cross-Design to search for trade-offs between environments.

How to read the results

Lower energy means better compatibility with the chosen helical state within the model. A more negative Z-score means the sequence is better than the random-sequence background. Percentile tells you where the sequence sits relative to that random ensemble, with lower being better. Net charge follows the current model convention; in this version histidine is treated as neutral in the charge-dependent terms.

What environments mean

Homogeneous polar approximates a water-like medium. Homogeneous apolar approximates a non-polar medium. Interfacial modes impose a membrane-facing and water-facing sector on the helical wheel, plus an anionic, neutral or cationic membrane surface charge. In the app, penetration depth is shown as a percentage, so it acts as an operational proxy for how much of the helix is exposed to the non-polar side of the interface.

What λgap means

λgap is only used in Cross-Design. It penalizes sequences that behave very differently in the two chosen environments. Small values favor the best overall compromise; larger values push the search toward more balanced cross-environment compatibility.

Hamiltonian terms

H = λ_envH_env + λ_chgH_chg + λ_μH_μ + λ_localH_local + λ_pairH_pair + λ_elecH_elec + λ_neighH_neigh

Environment rewards residues that match the target medium. Charge captures residue preference with membrane surface charge. Hydrophobic moment favors amphipathic segregation on the helix. Local helix and Helix neighbors reward helical propensity. Pairwise adds sequence-dependent interaction preferences. Electrostatics captures attractive and repulsive charge interactions along the helix. In the current parameterization, histidine contributes through the hydrophobicity and helical-propensity terms but is neutral in the charge-dependent terms.

Practical limitations

The model scores compatibility with a predefined helical scaffold. It is best interpreted as a relative design and ranking tool. Experimental activity, folding kinetics, insertion depth and membrane disruption require additional validation.

Score a Sequence

Estimate relative compatibility of a sequence with a predefined helical state in a selected environment.

Reference peptide Curated literature-inspired reference helices. Selecting one fills the sequence automatically; the residue background stays at the default alphabet unless you edit it. Sequence

Allowed residues Environment preset Random reference size Number of random sequences used to estimate the background mean and standard deviation for the Z-score. Web limit: 2,000. Penetration depth Operational proxy for how much of the helix is exposed to the non-polar side of the interface. Current value: 50%.

Optimal Penetration

Scan penetration depth for one sequence in one interfacial environment and define the optimum as the most negative Z-score.

Reference peptide Curated literature-inspired reference helices. Selecting one fills the sequence automatically; the residue background stays at the default alphabet unless you edit it. Sequence

Allowed residues Interface type Random reference size Background size used for each sampled penetration. Web limit: 2,000.

Penetration scan The scan is fixed from 0% = homogeneous polar medium (water-like) to 100% = homogeneous apolar medium (chloroform-like), with the selected interfacial preset used at intermediate points. The web app samples this path every 5%, for a total of 21 points.

Design for One Environment

Run sequence-space simulated annealing against a single target environment.

Length Number of residues in the designed helix. Web limit: 40. Allowed residues Environment preset Optimization steps (classical simulated annealing) Number of Monte Carlo mutation steps used during the simulated-annealing search. Higher values let the optimizer test more sequence changes, usually improving exploration at the cost of longer runtime. Web limit: 50,000. Penetration depth Current value: 50%. Higher percentages correspond to stronger exposure to the non-polar side of the interface. Restarts Independent annealing runs from different random starting points. Web limit: 20.

Need heavier searches or custom large-scale runs? Please contact SIMBIOS.

Design a Family

Generate several unique low-energy candidates for the same environment instead of a single optimum.

Length Number of residues in each designed helix. Web limit: 40. Allowed residues Environment preset Family size Requested number of diverse low-energy candidates. If the search cannot find that many unique solutions, the returned family may be smaller. Web limit: 12. Penetration depth Current value: 50%. Used only for interfacial families and interpreted as non-polar exposure percentage. Optimization steps (classical simulated annealing) Number of Monte Carlo mutation steps used in each annealing run. More steps generally help each candidate settle into a better low-energy sequence, but they also make family generation slower. Web limit: 20,000. Restarts per candidate More restarts improve robustness but increase runtime. Web limit: 20.

Need larger families or heavier searches? Please contact SIMBIOS.

Compare Two Environments

Quantify environmental selectivity and compare the same sequence across two target states.

Reference peptide Curated literature-inspired reference helices. Selecting one fills the sequence automatically; the residue background stays at the default alphabet unless you edit it. Sequence

Allowed residues

Environment A Environment B Penetration depth A Current value: 50%. Used only if environment A is interfacial. Penetration depth B Current value: 50%. Used only if environment B is interfacial.

Cross-Environment Design

Optimize a joint objective with a gap penalty to search for environmentally robust helical sequences.

Length Number of residues in the designed helix. Web limit: 40. Allowed residues Environment A Environment B Penetration depth A Current value: 50%. Used only if environment A is interfacial. Penetration depth B Current value: 50%. Used only if environment B is interfacial. Optimization steps (classical simulated annealing) Number of Monte Carlo mutation steps in the joint simulated-annealing search. Larger values give the optimizer more chances to improve the sequence across both environments, but increase runtime. Web limit: 60,000. λgap Penalty applied when the same sequence behaves too differently in the two environments. Increase it to favor more balanced solutions. Web limit: 10. Restarts Independent optimization runs from different starting points. Web limit: 20.

For heavier cross-environment searches or custom campaigns, please contact SIMBIOS.

Export Ideal Helix PDB

Build an idealized alpha-helical PDB for a selected sequence and download or copy it.