arXiv subjects

Tanvi Ganapathy

Publications and source records attributed to Tanvi Ganapathy.

2 recordsLinked to original sources

arXiv2026

General Multimodal Protein Design Enables DNA-Encoding of Chemistry

Evolution is an extraordinary engine for enzymatic diversity, yet the chemistry it has explored remains a narrow slice of what DNA can encode. Deep generative models can design new proteins that bind ligands, but none have created enzymes without pre-specifying catalytic residues. We introduce DISCO (DIffusion for Sequence-structure CO-design), a multimodal model that co-designs protein sequence and 3D structure around arbitrary biomolecules, as well as inference-time scaling methods that optimize objectives across both modalities. Conditioned solely on reactive intermediates, DISCO designs diverse heme enzymes with novel active-site geometries. These enzymes catalyze new-to-nature carbene-transfer reactions, including alkene cyclopropanation, spirocyclopropanation, B-H, and C(sp$^3$)-H insertions, with high activities exceeding those of engineered enzymes. Random mutagenesis of a selected design further confirmed that enzyme activity can be improved through directed evolution. By providing a scalable route to evolvable enzymes, DISCO broadens the potential scope of genetically encodable transformations. Code is available at https://github.com/DISCO-design/DISCO.

cs.LG↗

arXiv2024

Finding high posterior density phylogenies by systematically extending a directed acyclic graph

Bayesian phylogenetics typically estimates a posterior distribution, or aspects thereof, using Markov chain Monte Carlo methods. These methods integrate over tree space by applying local rearrangements to move a tree through its space as a random walk. Previous work explored the possibility of replacing this random walk with a systematic search, but was quickly overwhelmed by the large number of probable trees in the posterior distribution. In this paper we develop methods to sidestep this problem using a recently introduced structure called the subsplit directed acyclic graph (sDAG). This structure can represent many trees at once, and local rearrangements of trees translate to methods of enlarging the sDAG. Here we propose two methods of introducing, ranking, and selecting local rearrangements on sDAGs to produce a collection of trees with high posterior density. One of these methods successfully recovers the set of high posterior density trees across a range of data sets. However, we find that a simpler strategy of aggregating trees into an sDAG in fact is computationally faster and returns a higher fraction of probable trees.

q-bio.PE↗