RetroBridge: Modeling Retrosynthesis with Markov Bridges at ICLR 2024

Conceitos essenciais

Modeling retrosynthesis with Markov bridges for accurate prediction of precursor molecules.

Resumo

Introduces the Markov Bridge Model for retrosynthesis planning.
Proposes RetroBridge as a template-free method for single-step retrosynthesis prediction.
Outperforms diffusion models in mapping intractable discrete distributions.
Achieves state-of-the-art results on standard benchmarks.
Future work includes addressing limitations and applying the model to multi-step planning.

Estatísticas

Each step in multi-step retrosynthesis planning requires accurate prediction of possible precursor molecules.
RetroBridge achieves state-of-the-art results on standard evaluation benchmarks.

Citações

"Our framework is based on the concept of a Markov bridge, a Markov process pinned at its endpoints."
"We propose RetroBridge, the first Markov Bridge Model for retrosynthesis modeling."

Principais Insights Extraídos De

RetroBridge

by Ilia Igashov... às arxiv.org 03-27-2024

https://arxiv.org/pdf/2308.16212.pdf

Perguntas Mais Profundas

How can RetroBridge be adapted to suggest specific sets of reactants, reagents, and reaction types?

RetroBridge can be adapted to suggest specific sets of reactants, reagents, and reaction types by incorporating additional context information into the sampling process. This context information can guide the generation of reactants towards desired sets based on known reaction types or reagents. Here are some ways to adapt RetroBridge for this purpose:

Contextual Conditioning: Include information about specific reactants, reagents, or reaction types as part of the input to the neural network φθ at each sampling step. By conditioning the sampling process on this additional context, RetroBridge can bias the generation of reactants towards the desired sets.

Guided Sampling: Introduce constraints or rules based on known reaction types or reagents to guide the sampling process. By incorporating domain knowledge into the sampling algorithm, RetroBridge can prioritize the generation of reactants that are consistent with the specified reactants, reagents, or reaction types.

Multi-Step Planning: Extend RetroBridge to handle multi-step retrosynthesis planning, where the model predicts a sequence of reactions leading to the target molecule. By incorporating information about specific reactants, reagents, and reaction types at each step of the planning process, RetroBridge can suggest tailored reaction pathways.

By adapting RetroBridge in these ways, it can provide more targeted and specific suggestions for reactants, reagents, and reaction types in chemical synthesis planning.

How can the probabilistic framework used in RetroBridge for other chemical modeling tasks?

The probabilistic framework used in RetroBridge has several implications for other chemical modeling tasks:

Modeling Uncertainty: The probabilistic framework allows RetroBridge to capture uncertainty in the prediction of reactants. This is crucial in chemical modeling tasks where the same product molecule can be synthesized using different sets of reactants and reagents. By modeling uncertainty, RetroBridge can provide a range of possible solutions with associated confidence levels.

Generating Diverse Solutions: The probabilistic formulation enables RetroBridge to generate diverse retrosynthetic pathways by sampling from the learned distribution. This is valuable in chemical modeling tasks where multiple valid solutions exist for a given problem. The model can explore different possibilities and provide a variety of potential solutions.

Handling Intractable Distributions: The probabilistic framework allows RetroBridge to approximate the dependency between two intractable discrete distributions. This capability is beneficial in chemical modeling tasks where the underlying distributions are complex and difficult to model directly.

Overall, the probabilistic framework used in RetroBridge enhances the flexibility, robustness, and interpretability of the model, making it applicable to a wide range of chemical modeling tasks beyond retrosynthesis planning.

How can the Markov Bridge Model be applied to image-to-image translation or protein binder design?

The Markov Bridge Model can be applied to image-to-image translation or protein binder design by adapting the framework to the specific characteristics of these tasks. Here's how the model can be utilized in these contexts:

Image-to-Image Translation: In image-to-image translation tasks, the Markov Bridge Model can learn the dependency between two distributions of images, such as mapping images from one domain to another. By defining transition matrices and sampling trajectories between images, the model can generate realistic translations while preserving important features and structures.

Protein Binder Design: In protein binder design, the Markov Bridge Model can be used to model the relationship between protein structures and potential binding molecules. By representing proteins and ligands as discrete distributions, the model can learn the dependency between these distributions and generate novel protein-ligand complexes with desired binding properties.

Contextual Information: Incorporating context information, such as known protein structures or binding sites, can guide the sampling process in protein binder design tasks. By conditioning the generation of ligands on specific protein features, the model can suggest tailored binding molecules for a given protein target.

By applying the Markov Bridge Model to image-to-image translation and protein binder design tasks, it can facilitate the generation of diverse and contextually relevant solutions in these domains.