Fragment Based Design Calculator

Design inputs

Enter fragment properties, linking assumptions, and potency.

Project name (optional)

Target (optional)

Assay type

Potency (nM)

Used for pX, LE, LLE, BEI, SEI.

Connections (links formed)

RotB is reduced by ~0.5 per connection.

MW adjustment (optional)

Apply merge correction (± g/mol).

cLogP adjustment (optional)

Apply synergy or polarity correction.

Keep example rows

Fragment	MW	cLogP	HBD	HBA	TPSA	RotB	Rings	HAC	Notes

Example data table

These example values are prefilled when “Keep example rows” is enabled.

Fragment	MW	cLogP	HBD	HBA	TPSA	RotB	Rings	HAC
Pyridine fragment	79.10	0.60	0	1	25.78	0	1	6
Phenyl linker	77.10	1.90	0	0	0.00	1	1	6
Amide cap	59.07	-0.40	1	1	29.10	1	0	4

Formulas used

Additive totals: Property_total = Σ Property_fragment + optional adjustment.
pX (from nM): pX = 9 − log10(nM), where X is IC50 or Kd.
Ligand efficiency (LE): LE = 1.37 · pX / HAC (HAC = heavy atom count).
Lipophilic ligand efficiency (LLE): LLE = pX − cLogP_final.
BEI: BEI = 1000 · pX / MW_final.
SEI proxy: SEI = 100 · pX / TPSA.
Rule-of-Three checks: MW ≤ 300, cLogP ≤ 3, HBD ≤ 3, HBA ≤ 3, RotB ≤ 3, TPSA ≤ 60.

These are screening heuristics. Confirm with experimental and computational workflows.

How to use this calculator

Enter your fragments as rows, including MW, cLogP, and polar counts.
Set the number of connections formed during merging or linking.
Optional: add MW and cLogP adjustments to reflect chemical changes.
Provide potency (IC50 or Kd) in nM to compute pX and efficiencies.
Press Calculate to view results above the form.
Export CSV for tables, or PDF for a quick report.

Design efficiency benchmarks

Early fragment programs often compare designs with simple, repeatable metrics. This calculator converts potency in nM to pX using pX = 9 − log10(nM), then derives atom- and property-normalized indicators. Use pIC50 or pKd consistently across projects to avoid mixing assay noise with chemistry changes.

Rule-of-Three coverage

Fragment-like quality is summarized with six checks: MW ≤ 300, cLogP ≤ 3, HBD ≤ 3, HBA ≤ 3, RotB ≤ 3, and TPSA ≤ 60. A pass score of 5/6 or 6/6 usually indicates compact, learnable chemistry. If TPSA exceeds 60, watch permeability and solubility trade-offs during growth.

Ligand efficiency signals

LE estimates binding efficiency per heavy atom using LE = 1.37·pX/HAC. For fragments, values around 0.30–0.50 are commonly considered strong starting points. A falling LE during optimization can be acceptable if the added atoms improve selectivity, stability, or synthetic tractability.

Lipophilicity balance with LLE

LLE is computed as pX − cLogP. Designs with LLE ≥ 3 often show potency not dominated by lipophilicity. When LLE drops below 3, consider replacing hydrophobes with polar vectors, reducing aromatic count, or adding hydrogen-bonding features that improve interaction geometry.

Normalization by size and surface

BEI scales pX by molecular weight: BEI = 1000·pX/MW. It helps compare a 250 g/mol merge against a 420 g/mol grown lead. SEI (proxy) relates pX to polar surface: SEI = 100·pX/TPSA. Low SEI may indicate excess polarity for the potency achieved.

Using exports in design reviews

Export CSV when you need the fragment table and summary for spreadsheets or ELNs. Export PDF when you want a compact snapshot for a slide appendix. Pair the interactive Plotly chart with the rule checks to triage ideas quickly, then validate the top candidates with measured solubility, microsomal stability, and permeability assays.

FAQs

1) What does “connections” mean in this calculator?

Connections approximate link formation during merging. The tool applies a small RotB reduction (~0.5 per connection) to reflect constrained designs.

2) Why does the tool use pX instead of raw nM potency?

pX linearizes potency on a log scale, making comparisons across orders of magnitude clearer and stabilizing efficiency metrics like LE and LLE.

3) Are the Rule-of-Three checks strict requirements?

No. They are fragment screening heuristics. Programs may accept exceptions when binding mode, selectivity, or chemistry constraints justify them.

4) How should I choose MW and cLogP adjustments?

Use adjustments to reflect known merge chemistry, such as leaving groups removed, rings fused, or polarity changes from bioisosteres, keeping your source consistent.

5) What LE and LLE values are considered good?

Many fragment teams target LE around 0.30–0.50 and LLE ≥ 3 as healthy starting points, but context and assay confidence always matter.

6) Can I use this for non-fragment leads?

Yes. The additive model is simplified, but the efficiency metrics and exports still help benchmark lead series and prioritize property-balanced designs.