arXiv subjects

Anisha Parsan

Publications and source records attributed to Anisha Parsan.

4 recordsLinked to original sources

arXiv2026

SwitchCraft: A Programmatic Framework for Designing State-Switching Proteins

Multistate mechanisms underlie many of the complex functions observed in natural proteins. The ability to rationally design multistate proteins would have transformative implications for many areas of biotechnology, yet lies beyond the capabilities of existing deep learning frameworks for protein design. To address this gap, we introduce SwitchCraft, a versatile and programmatic framework for designing state-switching proteins based on backpropagation through compositional design constraints parameterized by structure prediction models. In silico evaluations demonstrate success on a wide range of state-switching functional primitives, from allosteric regulation of motifs to discrimination of bound ligand identities. Using these primitives, we demonstrate an in silico strategy for de novo design of fluorescent biosensors to arbitrary small molecule analytes. These results position SwitchCraft at the inception of a powerful paradigm for higher-order functional protein design. Code is available at https://github.com/bjing2016/switchcraft.

q-bio.BM↗

arXiv2025

Mechanistic Interpretability of Antibody Language Models Using SAEs

Sparse autoencoders (SAEs) are a mechanistic interpretability technique that have been used to provide insight into learned concepts within large protein language models. Here, we employ TopK and Ordered SAEs to investigate autoregressive antibody language models, and steer their generation. We show that TopK SAEs can reveal biologically meaningful latent features, but high feature-concept correlation does not guarantee causal control over generation. In contrast, Ordered SAEs impose a hierarchical structure that reliably identifies steerable features, but at the expense of more complex and less interpretable activation patterns. These findings advance the mechanistic interpretability of domain-specific protein language models and suggest that, while TopK SAEs suffice for mapping latent features to concepts, Ordered SAEs are preferable when precise generative steering is required.

cs.LG↗

arXiv2025

BindEnergyCraft: Casting Protein Structure Predictors as Energy-Based Models for Binder Design

Protein binder design has been transformed by hallucination-based methods that optimize structure prediction confidence metrics, such as the interface predicted TM-score (ipTM), via backpropagation. However, these metrics do not reflect the statistical likelihood of a binder-target complex under the learned distribution and yield sparse gradients for optimization. In this work, we propose a method to extract such likelihoods from structure predictors by reinterpreting their confidence outputs as an energy-based model (EBM). By leveraging the Joint Energy-based Modeling (JEM) framework, we introduce pTMEnergy, a statistical energy function derived from predicted inter-residue error distributions. We incorporate pTMEnergy into BindEnergyCraft (BECraft), a design pipeline that maintains the same optimization framework as BindCraft but replaces ipTM with our energy-based objective. BECraft outperforms BindCraft, RFDiffusion, and ESM3 across multiple challenging targets, achieving higher in silico binder success rates while reducing structural clashes. Furthermore, pTMEnergy establishes a new state-of-the-art in structure-based virtual screening tasks for miniprotein and RNA aptamer binders.

cs.LG↗

arXiv2022

A Multi-tasking Model of Speaker-Keyword Classification for Keeping Human in the Loop of Drone-assisted Inspection

Audio commands are a preferred communication medium to keep inspectors in the loop of civil infrastructure inspection performed by a semi-autonomous drone. To understand job-specific commands from a group of heterogeneous and dynamic inspectors, a model must be developed cost-effectively for the group and easily adapted when the group changes. This paper is motivated to build a multi-tasking deep learning model that possesses a Share-Split-Collaborate architecture. This architecture allows the two classification tasks to share the feature extractor and then split subject-specific and keyword-specific features intertwined in the extracted features through feature projection and collaborative training. A base model for a group of five authorized subjects is trained and tested on the inspection keyword dataset collected by this study. The model achieved a 95.3% or higher mean accuracy in classifying the keywords of any authorized inspectors. Its mean accuracy in speaker classification is 99.2%. Due to the richer keyword representations that the model learns from the pooled training data, adapting the base model to a new inspector requires only a little training data from that inspector, like five utterances per keyword. Using the speaker classification scores for inspector verification can achieve a success rate of at least 93.9% in verifying authorized inspectors and 76.1% in detecting unauthorized ones. Further, the paper demonstrates the applicability of the proposed model to larger-size groups on a public dataset. This paper provides a solution to addressing challenges facing AI-assisted human-robot interaction, including worker heterogeneity, worker dynamics, and job heterogeneity.

cs.SD↗