Predicting Protein-Ligand Docking Structure with Graph Neural Network.

Modern day drug discovery is extremely expensive and time consuming. Although computational approaches help accelerate and decrease the cost of drug discovery, existing computational software packages for docking-based drug discovery suffer from both low accuracy and high latency. A few recent machine learning-based approaches have been proposed for virtual screening by improving the ability to evaluate protein-ligand binding affinity, but such methods rely heavily on conventional docking software to sample docking poses, which results in excessive execution latencies. Here, we propose and evaluate a novel graph neural network (GNN)-based framework, MedusaGraph, which includes both pose-prediction (sampling) and pose-selection (scoring) models. Unlike the previous machine learning-centric studies, MedusaGraph generates the docking poses directly and achieves from 10 to 100 times speedup compared to state-of-the-art approaches, while having a slightly better docking accuracy.

A randomized controlled trial of two schedules of hepatitis B vaccination in predialysed chronic renal failure patients.

BACKGROUND: Patients with chronic renal disease should be vaccinated as soon as dialysis is forestalled, and this could improve the seroconversion of hepatitis B vaccination. OBJECTIVES: In this study, we aimed to compare seroconversion and immune response rates using 4 doses of 40 µg and 3 doses of 20 µg Euvax B recombinant Hepatitis B surface Antigen (HBs Ag) vaccine administered to predialysis patients with chronic kidney disease (CKD). PATIENTS AND METHODS: In an open, randomized clinical trial, we compared seroconversion rates in 51 predialysis patients with mild and moderate chronic renal failure who received either 4 doses of 40 µg or 3 doses of 20 µg of Euvax B recombinant hepatitis B vaccine administered at 0, 1, 2, 6 and 0, 1, 6 months, respectively. RESULTS: Differences in seroconversion rates after 4 doses of 40 µg (80.88%) compared to 3 doses of 20 µg (92%) were not significant (P = 0.4124). The mean HBs antibody level after 4 doses of 40 µg at 0, 1, 2, and 6 months (182.2 ± 286.7) was significantly higher than that after 3 doses of 40 µg at 0,1, and 6 months (96.9 ± 192.1) (P = 0.004). Seroconversion after 4 doses of 40 µg (80.8%) was also significantly higher than that after 3 doses of 40 µg (77%) (P = 0.004). Multivariable analysis showed that none of the variables contributed to seroconversion. CONCLUSIONS: We found that 4 doses of 40 µg did not lead to significantly more seroconversion than 3 doses of 20 µg.