Chemical Science最新文献_第9页

3DSMILES-GPT: 3D molecular pocket-based generation with token-only large language model.

IF 7.6 1区化学

Chemical Science Pub Date : 2024-12-04 DOI: 10.1039/d4sc06864e

Jike Wang, Hao Luo, Rui Qin, Mingyang Wang, Xiaozhe Wan, Meijing Fang, Odin Zhang, Qiaolin Gou, Qun Su, Chao Shen, Ziyi You, Liwei Liu, Chang-Yu Hsieh, Tingjun Hou, Yu Kang

{"title":"3DSMILES-GPT: 3D molecular pocket-based generation with token-only large language model.","authors":"Jike Wang, Hao Luo, Rui Qin, Mingyang Wang, Xiaozhe Wan, Meijing Fang, Odin Zhang, Qiaolin Gou, Qun Su, Chao Shen, Ziyi You, Liwei Liu, Chang-Yu Hsieh, Tingjun Hou, Yu Kang","doi":"10.1039/d4sc06864e","DOIUrl":"10.1039/d4sc06864e","url":null,"abstract":"The generation of three-dimensional (3D) molecules based on target structures represents a cutting-edge challenge in drug discovery. Many existing approaches often produce molecules with invalid configurations, unphysical conformations, suboptimal drug-like qualities, limited synthesizability, and require extensive generation times. To address these challenges, we present 3DSMILES-GPT, a fully language-model-driven framework for 3D molecular generation that utilizes tokens exclusively. We treat both two-dimensional (2D) and 3D molecular representations as linguistic expressions, combining them through full-dimensional representations and pre-training the model on a vast dataset encompassing tens of millions of drug-like molecules. This token-only approach enables the model to comprehensively understand the 2D and 3D characteristics of large-scale molecules. Subsequently, we fine-tune the model using pair-wise structural data of protein pockets and molecules, followed by reinforcement learning to further optimize the biophysical and chemical properties of the generated molecules. Experimental results demonstrate that 3DSMILES-GPT generates molecules that comprehensively outperform existing methods in terms of binding affinity, drug-likeness (QED), and synthetic accessibility score (SAS). Notably, it achieves a 33% enhancement in the quantitative estimation of QED, meanwhile the binding affinity estimated by Vina docking maintaining its state-of-the-art performance. The generation speed is remarkably fast, with the average time approximately 0.45 seconds per generation, representing a threefold increase over the fastest existing methods. This innovative 3DSMILES-GPT approach has the potential to positively impact the generation of 3D molecules in drug discovery.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fast synthesis of DNA origami single crystals at room temperature

IF 8.4 1区化学

Chemical Science Pub Date : 2024-12-04 DOI: 10.1039/d4sc07267g

Yifan Yu, Min Ji, Yong Wang, Xuehui Yan, Lizhi Dai, Ningning Ma, Zhaoyu Zhou, Hang Xing, Ye Tian

{"title":"Fast synthesis of DNA origami single crystals at room temperature","authors":"Yifan Yu, Min Ji, Yong Wang, Xuehui Yan, Lizhi Dai, Ningning Ma, Zhaoyu Zhou, Hang Xing, Ye Tian","doi":"10.1039/d4sc07267g","DOIUrl":"https://doi.org/10.1039/d4sc07267g","url":null,"abstract":"Structural DNA nanotechnology makes the programmable design and assembly of DNA building blocks into user-defined microstructures feasible. However, the formation and further growth of these microstructures requires slow heat treatment in precise instruments, as otherwise amorphous aggregates result. Here, we used an organic solute, urea, as the catalyst for the crystallization of DNA origami building blocks to achieve the fast synthesis of DNA origami single crystals with a cubic Wulff shape at room temperature. The ordered assemblies can be formed within 4 hours at room temperature, which further grew into cubic microcrystals with an average size of about 5 micrometers within 2 days. Furthermore, the phase diagram provides an inverse logic that allows users to proactively customize the melting temperature (Tm) of crystallization according to the target temperature conditions, rather than requiring de novo design of DNA sequences or painstakingly difficult trial-and-error attempts. On this basis, even under random fluctuating outdoor temperature conditions, DNA origami crystals can still grow and maintain high quality and high yield comparable to those of crystals synthesized in precise instruments, creating a basis for the development of adaptive self-assemblies and the industrialization of functional DNA microstructures.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"27 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Magic methylation with methyl-containing peroxides

IF 8.4 1区化学

Chemical Science Pub Date : 2024-12-04 DOI: 10.1039/d4sc05620e

Daliah Farajat, Yuhua Zhang, Chao-Jun Li

引用次数: 0

Correction: Ion pair extractant selective for LiCl and LiBr

IF 7.6 1区化学

Chemical Science Pub Date : 2024-12-04 DOI: 10.1039/D4SC90238F

Nam Jung Heo, Ju Hyun Oh, Aimin Li, Kyounghoon Lee, Qing He, Jonathan L. Sessler and Sung Kuk Kim

引用次数: 0

DiffBP: Generative Diffusion of 3D Molecules for Target Protein Binding

IF 8.4 1区化学

Chemical Science Pub Date : 2024-12-04 DOI: 10.1039/d4sc05894a

Haitao Lin, Yufei Huang, Odin Zhang, Siqi Ma, Meng Liu, Xuanjing Li, Lirong Wu, Shuiwang Ji, Tingjun Hou, Stan Z. Q. Li

{"title":"DiffBP: Generative Diffusion of 3D Molecules for Target Protein Binding","authors":"Haitao Lin, Yufei Huang, Odin Zhang, Siqi Ma, Meng Liu, Xuanjing Li, Lirong Wu, Shuiwang Ji, Tingjun Hou, Stan Z. Q. Li","doi":"10.1039/d4sc05894a","DOIUrl":"https://doi.org/10.1039/d4sc05894a","url":null,"abstract":"Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Most previous works typically generate atoms autoregressively, with element types and 3D coordinates of atoms generated sequentially. However, in real-world molecular systems, atomic interactions span the entire molecule, necessitating a consideration of pairwise-additive energy among atoms. Given this energy-centric perspective, modeling probability should rely on joint distributions instead of sequential conditional ones. Thus, the conventional sequential auto-regressive methods for molecule generation can inadvertently violate physical principles, yielding molecules with undesirable properties. In this study, we propose DiffBP, a generative diffusion model that generates 3-dimensional (3D) molecular structures, leveraging target proteins as contextual constraints at the full-atom level in a non-autoregressive way. When provided with a specified 3D protein binding site, our model learns to denoise both the element types and 3D coordinates of the entire molecule using an equivariant network. Experimental assessments illustrate that DiffBP performs competitively against existing methods, generating molecules with high protein affinity, appropriate molecule sizes, and desirable drug-like profiles. Additionally, we develop a website server for medicinal chemists interested in exploring the art of molecular generation, which is accessible at http://www.manimer.com/moleculeformation/index.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"27 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mimic Metalloenzymes with Atomically Dispersed Fe Sites into Covalent Organic Framework Membranes for Enhanced CO2 Photoreduction

IF 8.4 1区化学

Chemical Science Pub Date : 2024-12-03 DOI: 10.1039/d4sc05999a

Shuaiqi Gao, Xiao Zhao, Qian Zhang, Linlin Guo, Zhiyong Li, Huiyong Wang, Suojiang Zhang, Jianji Wang

{"title":"Mimic Metalloenzymes with Atomically Dispersed Fe Sites into Covalent Organic Framework Membranes for Enhanced CO2 Photoreduction","authors":"Shuaiqi Gao, Xiao Zhao, Qian Zhang, Linlin Guo, Zhiyong Li, Huiyong Wang, Suojiang Zhang, Jianji Wang","doi":"10.1039/d4sc05999a","DOIUrl":"https://doi.org/10.1039/d4sc05999a","url":null,"abstract":"The massive CO2 emissions from continuous increases in fossil fuel consumption have caused disastrous environmental and ecological crises. Covalent organic frameworks (COFs) hold the potential to convert CO2 and water into value-added chemicals and O2 to mitigate this crisis. However, their activity and selectivity are very low under conditions close to natural photosynthesis. In this work, inspired by the photosynthesis process in natural leaves, we successfully anchored atomically dispersed Fe sites into interlayers of the photoactive triazine-based COF (Fe-COF) membrane to serve as a mimic metalloenzyme for the first time. It is found that under the conditions of gas-solid and no addition of any photosensitizer and sacrificial reagent, the highly crystalline Fe-COF membrane shows a record high CO2 photoreduction performance with the CO production of 3972 μmol g-1 in a 4 h reaction, ~100% selectivity of CO, and excellent cycling stability (at least 10 cycles). In such a remarkable photocatalytic CO2 conversion, the atomically dispersed Fe sites with high catalytic activity significantly reduce the formation energy barrier of key *CO2 and *COOH intermediates, the high-density triazine moieties supply more electrons to the iron catalytic center to promote CO2 reduction, and the homogeneous COF membrane greatly improves the electron/mass transport. Thus, this work opens a new window for the design of highly efficient photocatalysts and provides new insights into their structure-activity relationship in CO2 photocatalytic reduction.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"12 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The energetic landscape of CH-π interactions in protein-carbohydrate binding.

IF 7.6 1区化学

Chemical Science Pub Date : 2024-12-03 DOI: 10.1039/d4sc06246a

Allison M Keys, David W Kastner, Laura L Kiessling, Heather J Kulik

{"title":"The energetic landscape of CH-π interactions in protein-carbohydrate binding.","authors":"Allison M Keys, David W Kastner, Laura L Kiessling, Heather J Kulik","doi":"10.1039/d4sc06246a","DOIUrl":"10.1039/d4sc06246a","url":null,"abstract":"CH-π interactions between carbohydrates and aromatic amino acids play an essential role in biological systems that span all domains of life. Quantifying the strength and importance of these CH-π interactions is challenging because these interactions involve several atoms and can exist in many distinct orientations. To identify an orientational landscape of CH-π interactions, we constructed a dataset of close contacts formed between β-d-galactose residues and the aromatic amino acids, tryptophan, tyrosine, and phenylalanine, across crystallographic structures deposited in the Protein Data Bank. We carried out quantum mechanical calculations to quantify their interaction strengths. The data indicate that tryptophan-containing CH-π interactions have more favorable interaction energies than those formed by tyrosine or phenylalanine. The energetic differences between these amino acids are caused by the aromatic ring system electronics and size. We use individual distance and angle features to train random forest models to successfully predict the first-principles computed energetics of CH-π interactions. Using insights from our models, we define a tradeoff in CH-π interaction strength arising from the proximity of galactose carbons 1 and 2 versus carbons 4 and 6 to the aromatic amino acid. Our work demonstrates that a feature of CH-π stacking interactions is that numerous orientations allow for highly favorable interaction strengths.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Internally diketopyrrolopyrrole-bridged bis-anthracene macrocycle: A multifunctional fluorescent platform

IF 8.4 1区化学

Chemical Science Pub Date : 2024-12-03 DOI: 10.1039/d4sc06067a

Huan Zhou, Yuxuan Zhang, Zhiye Zheng, Jun-Hua Wan, Hui Zhang, Kunhua Lin, Jonathan L. Sessler, Hong-Yu Wang

{"title":"Internally diketopyrrolopyrrole-bridged bis-anthracene macrocycle: A multifunctional fluorescent platform","authors":"Huan Zhou, Yuxuan Zhang, Zhiye Zheng, Jun-Hua Wan, Hui Zhang, Kunhua Lin, Jonathan L. Sessler, Hong-Yu Wang","doi":"10.1039/d4sc06067a","DOIUrl":"https://doi.org/10.1039/d4sc06067a","url":null,"abstract":"A covalently bridged macrocycle architecture (5) comprising two anthracene strands that connect at the lactam positions of a diketopyrrolopyrrole (DPP) chromophore has been constructed. The crystal structure reveals that the central DPP chromophore is wrapped by the external twisted bis-anthracene macrocycle. The internally bridged macrocycle architecture endows 5 with multifunctional properties. Due to shielding by the double anthracene straps, 5a and a polymer derived from it, DPP-Cycle, display strong fluorescence emission features in both organic media and the solid state. Moreover, the emission colors of these macrocyclic materials can be effectively tuned by external stimuli such as mechanical and thermal treatments, as well as solvent fuming. Compound 5a is stable in the presence of most metal cations but degrades rapidly when contacted with Cu2+ in acetonitrile. This decomposition, which is thought to involve a reaction at the central DPP via a radical-mediated mechanism, was found to be accelerated in 5a compared to the non-cyclic analogue 2a. This leads us to suggest that internally bridged macrocycles, such as those described here, may have a role to play as fluorescent Cu2+ sensors. Finally, the high fluorescence of 5a in the solid state allows for its use in the area of latent fingerprint (LFP) imaging.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"9 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sub-m-benziporphyrin: A Subcarbaporphyrinoid and Its BIII Complex with An Unprecedented Planar Tridentate 14-Aromatic Network

IF 8.4 1区化学

Chemical Science Pub Date : 2024-12-03 DOI: 10.1039/d4sc07199a

Le Liu, Shuangji Song, Jiyeon Lee, Yutao Rao, Ling Xu, Mingbo Zhou, Bangshao Yin, Juwon Oh, Jiwon Kim, Atsuhiro Osuka, Jianxin Song

引用次数: 0

MXene-based Solvent-responsive Actuators with a Polymer-intercalated Gradient Structure

IF 8.4 1区化学

Chemical Science Pub Date : 2024-12-03 DOI: 10.1039/d4sc04935g

Andi Di, Chenlu Wang, Yanlei Wang, Hongyan He, Wentao Deng, Pierre Stiernet, Lennart Bergström, Jiayin Yuan, Miao Zhang

{"title":"MXene-based Solvent-responsive Actuators with a Polymer-intercalated Gradient Structure","authors":"Andi Di, Chenlu Wang, Yanlei Wang, Hongyan He, Wentao Deng, Pierre Stiernet, Lennart Bergström, Jiayin Yuan, Miao Zhang","doi":"10.1039/d4sc04935g","DOIUrl":"https://doi.org/10.1039/d4sc04935g","url":null,"abstract":"Actuators based on electrically conductive and hydrophilic two-dimensional (2D) Ti3C2TX MXene are of interest for fast and specific response in demanding environments, such a chemical production. Herein, Ti3C2TX-based solvent-responsive bilayer actuators were developed, featuring a gradient polymer-intercalation structure in the active layer. These actuator were assembled using negatively charged pristine Ti3C2TX nanosheets for the passive layer and positively charged polymer-tethered Ti3C2TX for the active layer. 2D wide-angle X-ray scattering and simulations related the gradient polymer intercalated microstructure in the polymer/MXene composite active layer to the counterintuitive actuation behavior. The bending of the bilayer films in solvent vapor is triggered by the gradient polymer-intercalation and the differing diffusion rate of solvent molecules through the MX and MX-polymer layers of the bilayer actuator. With their ease of fabrication, remote light-control capabilities, and excellent actuation performance, the Ti3C2TX-based bilayer actuators reported here may find applications in areas such as sensors for monitoring chemical production, infrared camouflage, smart switches, and excavators in toxic solvent environments.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"90 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0