Lin Gu

Fukang Ge, Jiarui Zhu, Linjie Zhang et al.

Modern AI technologies for drug discovery are distributed across heterogeneous platforms-including web applications, desktop environments, and code libraries-leading to fragmented workflows, inconsistent interfaces, and high integration overhead. We present an agentic end-to-end drug design framework that leverages a Large Language Model (LLM) in conjunction with the Model Context Protocol (MCP) to dynamically coordinate access to biochemical databases, modular toolchains, and task-specific AI models. The system integrates four state-of-the-art components: MaSIF (MaSIF-site and MaSIF-seed-search) for geometric deep learning-based identification of protein-protein interaction (PPI) sites, Rosetta for grafting protein fragments onto protein backbones to form mini proteins, ProteinMPNN for amino acid sequences redesign, and AlphaFold3 for near-experimental accuracy in complex structure prediction. Starting from a target structure, the framework supports de novo binder generation via surface analysis, scaffold grafting and pose construction, sequence optimization, and structure prediction. Additionally, by replacing rigid, script-based workflows with a protocol-driven, LLM-coordinated architecture, the framework improves reproducibility, reduces manual overhead, and ensures extensibility, portability, and auditability across the entire drug design process.

Wasif Khan, Lin Gu, Noah Hammarlund et al.

Physical activity is a modifiable lifestyle factor with potential to support cognitive resilience. However, the association of moderate-to-vigorous physical activity (MVPA) intensity, and timing, with cognitive function and region-specific brain structure remain poorly understood. We analyzed data from 45,892 UK Biobank participants aged 60 years and older with valid wrist-worn accelerometer data, cognitive testing, and structural brain MRI. MVPA was measured both continuously (mins per week) and categorically (thresholded using >=150 min/week based on WHO guidelines). Associations with cognitive performance and regional brain volumes were evaluated using multivariable linear models adjusted for demographic, socioeconomic, and health-related covariates. We conducted secondary analyses on MVPA timing and subgroup effects. Higher MVPA was associated with better performance across cognitive domains, including reasoning, memory, executive function, and processing speed. These associations persisted in fully adjusted models and were higher among participants meeting WHO guidelines. Greater MVPA was also associated with subcortical brain regions (caudate, putamen, pallidum, thalamus), as well as regional gray matter volumes involved in emotion, working memory, and perceptual processing. Secondary analyses showed that MVPA at any time of day was associated with cognitive functions and brain volume particularly in the midday-afternoon and evening. Sensitivity analysis shows consistent findings across subgroups, with evidence of dose-response relationships. Higher MVPA is associated with preserved brain structure and enhanced cognitive function in later life. Public health strategies to increase MVPA may support healthy cognitive aging and generate substantial economic benefits, with global gains projected to reach USD 760 billion annually by 2050.