BInD: Bond and Interaction-generating Diffusion Model for Multi-objective Structure-based Drug Design

Fuente: arXiv
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Hauptverfasser: Lee, Joongwon, Zhung, Wonho, Seo, Jisu, Kim, Woo Youn
Format: Preprint
Veröffentlicht: 2024
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author Lee, Joongwon
Zhung, Wonho
Seo, Jisu
Kim, Woo Youn
author_facet Lee, Joongwon
Zhung, Wonho
Seo, Jisu
Kim, Woo Youn
contents Recent remarkable advancements in geometric deep generative models, coupled with accumulated structural data, enable structure-based drug design (SBDD) using only target protein information. However, existing models often struggle to balance multiple objectives, excelling only in specific tasks. BInD, a diffusion model with knowledge-based guidance, is introduced to address this limitation by co-generating molecules and their interactions with a target protein. This approach ensures balanced consideration of key objectives, including target-specific interactions, molecular properties, and local geometry. Comprehensive evaluations demonstrate that BInD achieves robust performance across all objectives, matching or surpassing state-of-the-art methods. Additionally, an NCI-driven molecule design and optimization method is proposed, enabling the enhancement of target binding and specificity by elaborating the adequate interaction patterns.
format Preprint
id arxiv_https___arxiv_org_abs_2405_16861
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle BInD: Bond and Interaction-generating Diffusion Model for Multi-objective Structure-based Drug Design
Lee, Joongwon
Zhung, Wonho
Seo, Jisu
Kim, Woo Youn
Biomolecules
Machine Learning
Biological Physics
Recent remarkable advancements in geometric deep generative models, coupled with accumulated structural data, enable structure-based drug design (SBDD) using only target protein information. However, existing models often struggle to balance multiple objectives, excelling only in specific tasks. BInD, a diffusion model with knowledge-based guidance, is introduced to address this limitation by co-generating molecules and their interactions with a target protein. This approach ensures balanced consideration of key objectives, including target-specific interactions, molecular properties, and local geometry. Comprehensive evaluations demonstrate that BInD achieves robust performance across all objectives, matching or surpassing state-of-the-art methods. Additionally, an NCI-driven molecule design and optimization method is proposed, enabling the enhancement of target binding and specificity by elaborating the adequate interaction patterns.
title BInD: Bond and Interaction-generating Diffusion Model for Multi-objective Structure-based Drug Design
topic Biomolecules
Machine Learning
Biological Physics
url https://arxiv.org/abs/2405.16861