Recent advances in large language models (LLMs) have demonstrated exceptional performance in protein-ligand interaction prediction, but state-of-the-art pipelines for large-scale virtual screening almost exclusively rely on high-end GPU clusters with hundreds of gigabytes of memory, creating prohibitive hardware barriers for small academic teams. In this work, we present a fully local low-resource framework that deploys the 175-billion-parameter DeepSeek 175B LLM on a single consumer-grade RTX 4060 laptop equipped with 32GB system RAM and 8GB VRAM, completing a full 200k-scale protein-ligand virtual screening workflow across 20 distinct protein targets. Our implementation achieves 100x throughput of an 8-card A100 cluster baseline under identical task configurations within 72 hours, with an average binding affinity prediction error of 0.88 kcal/mol across all targets, satisfying the 1.0 kcal/mol chemical accuracy requirement for preclinical drug discovery. Systematic runtime profiling reveals that heterogeneous memory management overhead accounts for 72% of total execution time, while accuracy loss introduced by model optimization contributes less than 10% to total prediction error. This work validates the engineering feasibility of running industrial-scale trillion-parameter LLM-driven biomedical computing tasks on consumer hardware, establishing a new low-barrier paradigm for AI-powered early stage drug discovery.
Generative molecular models for drug design are a promising direction with much active research. In the next phase of computational drug design, such models will need to understand small molecule structure and protein-ligand interactions, and they will need to possess the machinery to generate molecules de novo. Incorporating each feature poses a critical challenge. Equally important, yet often treated as secondary, is the ability to grow a molecule from a partial starting point -- a scaffold or fragment supplied by a chemist -- which is the central operation of lead optimization. We present Sesame (Spatial Evoformer for a Structure-Aware Molecular Engine), a diffusion-based molecular generation model that leverages a novel spatial pairformer module to condition on partial molecular structure and the surrounding protein pocket, both expressed as continuous spatial density maps. This single conditioning mechanism supports both de novo generation and fragment-conditioned lead optimization, letting a medicinal chemist prune a hit to a scaffold and have Sesame grow it in productive ways. In addition to this module, we also introduce a diffusion framework for joint denoising of atom types, bond types, and positions, along with a trajectory finetuning scheme that trains on the model's own sampling rollouts to improve generation quality. Sesame is trained on a large corpus of ligand-only and protein-ligand datasets.