GADIFF: a transferable graph attention diffusion model for generating molecular conformations.

Brief Bioinform

School of Information Science and Technology, Northeast Normal University, 130117 Changchun, China.

Published: November 2024

AI Article Synopsis

  • GADIFF is a novel graph attention diffusion model designed for generating molecular conformations, leveraging equivariant networks and self-attention mechanisms to enhance feature representation and noise prediction.
  • The model incorporates Graph Isomorphism Networks for capturing local interactions within molecular structures and demonstrates improved performance in generating diverse and accurate molecular conformations compared to existing state-of-the-art methods.
  • A derived model, GADIFF-NCI, extends GADIFF's capabilities to noncovalent interaction systems, showing effective conformation generation, indicating its potential for broader applications in studying complex molecular conformations.

Article Abstract

The diffusion generative model has achieved remarkable performance across various research fields. In this study, we propose a transferable graph attention diffusion model, GADIFF, for a molecular conformation generation task. With adopting multiple equivariant networks in the Markov chain, GADIFF adds GIN (Graph Isomorphism Network) to acquire local information of subgraphs with different edge types (atomic bonds, bond angle interactions, torsion angle interactions, long-range interactions) and applies MSA (Multi-head Self-attention) as noise attention mechanism to capture global molecular information, which improves the representative of features. In addition, we utilize MSA to calculate dynamic noise weights to boost molecular conformation noise prediction. Upon the improvements, GADIFF achieves competitive performance compared with recently reported state-of-the-art models in terms of generation diversity(COV-R, COV-P), accuracy (MAT-R, MAT-P), and property prediction for GEOM-QM9 and GEOM-Drugs datasets. In particular, on the GEOM-Drugs dataset, the average COV-R is improved by 3.75% compared with the best baseline model at a threshold (1.25 Å). Furthermore, a transfer model named GADIFF-NCI based on GADIFF is developed to generate conformations for noncovalent interaction (NCI) molecular systems. It takes GADIFF with GEOM-QM9 dataset as a pre-trained model, and incorporates a graph encoder for learning molecular vectors at the NCI molecular level. The resulting NCI molecular conformations are reasonable, as assessed by the evaluation of conformation and property predictions. This suggests that the proposed transferable model may hold noteworthy value for the study of multi-molecular conformations. The code and data of GADIFF is freely downloaded from https://github.com/WangDHg/GADIFF.

Download full-text PDF

Source
http://dx.doi.org/10.1093/bib/bbae676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684900PMC

Publication Analysis

Top Keywords

nci molecular
12
transferable graph
8
graph attention
8
attention diffusion
8
diffusion model
8
molecular
8
molecular conformations
8
molecular conformation
8
angle interactions
8
gadiff
7

Similar Publications

Background: Esophageal cancer (ESC) is an aggressive disease which often presents at an advanced stage. Despite trimodal therapy, 40-50% patients can develop metastatic disease by 18 months. Identification of patients at risk for metastatic spread is challenging with need for improved prognostication.

View Article and Find Full Text PDF

Tissue factor targeted near-infrared photoimmunotherapy: a versatile therapeutic approach for malignancies.

Cancer Immunol Immunother

January 2025

Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.

Tissue factor (TF) is a cell surface protein that plays a role in blood clotting but is also commonly expressed in many cancers. Recent research implicated TF in cancer proliferation, metastasis, angiogenesis, and immune escape. Therefore, TF can be considered a viable therapeutic target against cancer.

View Article and Find Full Text PDF

How does dopamine convert into norepinephrine? Insights on the key step of the reaction.

J Mol Model

January 2025

Laboratorio de Química Teórica Computacional (QTC), Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Avenida Vicuña Mackenna 4860, 7820436, Santiago de Chile, Chile.

Context: Dopamine -monooxygenase (D M) is an essential enzyme in the organism that regioselectively converts dopamine into R-norepinephrine, the key step of the reaction, studied in this paper, is a hydrogen atom transfer (HAT) from dopamine to a superoxo complex on D M, forming a hydroperoxo intermediate and dopamine radical. It was found that the formation of a hydrogen bond between dopamine and the D M catalyst strengthens the substrate-enzyme interaction and facilitates the HAT which takes place selectively to give the desired enantiomeric form of the product. Six reactions leading to the hydroperoxo intermediate were analyzed in detail using theoretical and computational tools in order to identify the most probable reaction mechanism.

View Article and Find Full Text PDF

Background: Synaptic loss predicts cognitive decline in Alzheimer's disease (AD). However, the critical disease modifying molecular mechanisms of synaptic failure remain elusive. Animal studies implicate the increased activation of cytosolic phospholipase (cPLA2) activation in synaptic loss and neuroinflammation.

View Article and Find Full Text PDF

Prostate fibrosis contributes to lower urinary tract dysfunction (LUTD). To develop targeted treatments for prostate fibrosis, it is necessary to identify cell types and molecular pathways required for collagen production. We used a genetic approach to label and track potential collagen-producing cell lineages in mouse prostate through a round of Escherichia coli (E.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!