Papers › General Binding Affinity Guidance for Diffusion Models in Structure-Based Drug Design

General Binding Affinity Guidance for Diffusion Models in Structure-Based Drug Design

24 Jun 2024arXiv:2406.16821archive 2025-07-28

Yue Jian, Curtis Wu, Danny Reidenbach, Aditi S. Krishnapriyan

Structure-Based Drug Design (SBDD) focuses on generating valid ligands that strongly and specifically bind to a designated protein pocket. Several methods use machine learning for SBDD to generate these ligands in 3D space, conditioned on the structure of a desired protein pocket. Recently, diffusion models have shown success here by modeling the underlying distributions of atomic positions and types. While these methods are effective in considering the structural details of the protein pocket, they often fail to explicitly consider the binding affinity. Binding affinity characterizes how tightly the ligand binds to the protein pocket, and is measured by the change in free energy associated with the binding process. It is one of the most crucial metrics for benchmarking the effectiveness of the interaction between a ligand and protein pocket. To address this, we propose BADGER: Binding Affinity Diffusion Guidance with Enhanced Refinement. BADGER is a general guidance method to steer the diffusion sampling process towards improved protein-ligand binding, allowing us to adjust the distribution of the binding affinity between ligands and proteins. Our method is enabled by using a neural network (NN) to model the energy function, which is commonly approximated by AutoDock Vina (ADV). ADV's energy function is non-differentiable, and estimates the affinity based on the interactions between a ligand and target protein receptor. By using a NN as a differentiable energy function proxy, we utilize the gradient of our learned energy function as a guidance method on top of any trained diffusion model. We show that our method improves the binding affinity of generated ligands to their protein receptors by up to 60\%, significantly surpassing previous machine learning methods. We also show that our guidance method is flexible and can be easily applied to other diffusion-based SBDD frameworks.

Code

Repository list and official/mentioned flags are the archive's, frozen 2025-07-28. Reachability, where shown, is from one Syntology probe window (2026-09-16 to 2026-09-18); repositories not probed show nothing. GitHub stars are not tracked.

Code Syntology ran Syntology

8 samples harvested; 2 ran; 2 honoured the contract we drafted; 6 have no recorded run. Read from Syntology's graph 2026-09-24; that is when this build read the record, not when the samples ran.

Licence: 0 of the 8 samples are pointer only, meaning Syntology does not serve that copy's text. This page shows no code text for any sample; each one links to its file in the repository.

Harvested from ask-berkeley/badger-sbdd. “Ran” means the sample executed on a synthesized input. It does not mean the output is correct, and nothing here reproduces the paper's results. “Honoured” and “violated” refer to a contract Syntology drafted from the code itself; “our draft was wrong” and “fixture could not drive it” are failures of Syntology's instrument, not of the code.

Each sample ends with its code_sha256, Syntology's identity for that exact code. An agent fetches the stored sample with Syntology's MCP tool get_code(code_sha256="…") (how to connect); click an identity to copy that call.

Repository labels, per sample. official repository: The archive marks this repository official for the paper. named in the paper: The archive records that the paper mentions this repository; it is not marked official. community (archive-listed): In the archive's code links for this paper, not marked official and not recorded as mentioned in the paper. found in paper text by Syntology: Syntology found this repository in the paper's own text; whether it is the authors' implementation is not asserted. community: Not in the archive's code links for this paper; a community repository Syntology harvested. Samples from a repository marked official are listed first. Licence labels name the repository's licence as recorded at harvest. “Pointer only” means Syntology does not serve that copy's text, for one of four reasons: no licence file was found; the licence was not identified; the licence is recorded as permissive but that copy's record is not marked cleared; or the licence is outside the permissive list Syntology serves text under (MIT, Apache-2.0, BSD and similar). Some licences outside that list permit redistribution, such as WTFPL, and GPL-3.0 under its conditions; they are simply not on the list. Hover a licence label for the reason. File links open the file on GitHub at the default branch, which may have changed since the harvest.

Tasks

Results from the paper archive 2025-07-28

No leaderboard rows for this paper in the archive.

Methods

Report a problem or propose a change · a person checks every report against the paper or source before anything changes; decisions are listed on /corrections