Solution modality / Small Molecules

Design around the effect, not only the binding pose.

Investigate a molecular route through binding geometry, conformational access and chemistry, then ask whether selectivity and exposure support the intended effect.

Current work Computational design studies

Explore this approach for your program Compare solution modalities

What must binding change?

Compare a binding or reaction hypothesis and determine which chemical design and assay could test it.

Mechanisms in scope

  • Reversible noncovalent binders and modulators
  • Cysteine-directed covalent compounds
  • Non-cysteine covalent compounds
  • Reversible-covalent compounds
  • Allosteric, PPI and conformational modulators
  • RNA-structure ligands, including rG4

From molecular proposal to candidate evidence

  • In BioTwin today · Computational methods cover selected binding, covalent chemistry, allostery and RNA-structure questions. A focused evaluation establishes which methods fit your target and inputs.
  • Development and validation · Selected branches have computational studies, calibration results and candidate designs. Each result carries its own comparison and validation scope; biological activity is a separate experimental question.

Choose the experiment that could change the design

Start with the relevant target states and a measurable molecular effect. Compare the most credible binding or reaction hypotheses, then choose chemistry and assays that can distinguish them.

Methods for this investigation

Relevant methods; exact support depends on the target, inputs and scientific route.

  • Boltzmann Ensemble Covalent Ligandability · Rank covalent sites by the joint presence of pocket fit, cysteine reactivity and sulfur exposure across a modeled conformational ensemble. Read the method
  • Topological Cryptic-Pocket Discovery · Localize candidate cryptic openings with persistent homology, then test access and conformational availability before treating them as binding sites. Read the method
  • Programmable Allostery · Search for bounded structural-network perturbations that produce a chosen protein response, then check the proposed change in a forward model. Read the method
  • RNA G-Quadruplex Targeting (rG4) · Connect RNA G-quadruplex formation, structural selectivity and concrete ligand-design questions, with evidence kept separate at each stage. Read the method
  • Non-Cysteine Covalent Design · Investigate residue and warhead alternatives when cysteine-directed engagement is unsuitable for the target. Read the method
  • Ligand-Induced pKa Design and Cation Placement · Investigate local cation placement, pKa shifts and reaction-rate compensation as a target-conditioned covalent-design strategy. Read the method

Discuss Small Molecules for your program

Start with the biological objective and the decision you need to make. We can establish which existing methods fit and what additional development would be required.

Discuss the research scope