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Deep Generative Models for 3D Compound Design [article]

Fergus Imrie, Anthony R Bradley, Mihaela van der Schaar, Charlotte M Deane
2019 bioRxiv   pre-print
We have developed a novel graph-based deep generative model that combines state-of-the-art machine learning techniques with structural knowledge.  ...  Computational generative methods have begun to show promising results for the design problem. However, they have not yet used the power of 3D structural information.  ...  Acknowledgement The authors thank Veerabahu Shanmugasundaram for helpful discussions on PROTACs. F.I. is supported by the EPSRC (Reference: EP/N509711/1).  ... 
doi:10.1101/830497 fatcat:qaygjew3tnbclmhpd6zrkyamy4

Deep generative design with 3D pharmacophoric constraints

Fergus Imrie, Thomas E. Hadfield, Anthony R. Bradley, Charlotte M. Deane
2021 Chemical Science  
A novel deep generative model combines convolution and graph neural networks to allow 3D-aware molecular design.  ...  We show how 3D pharmacophoric information can be incorporated into generative models and apply our model to both linker and R-group design.  ...  Results and discussion We validate the ability of our deep generative model (DEVELOP) to perform linker design and scaffold elaboration using 3D pharmacophoric information, reporting signicant improvement  ... 
doi:10.1039/d1sc02436a pmid:34881010 pmcid:PMC8580048 fatcat:dblmjbutfngulhirrgmmof2uhy

3DLinker: An E(3) Equivariant Variational Autoencoder for Molecular Linker Design [article]

Yinan Huang, Xingang Peng, Jianzhu Ma, Muhan Zhang
2022 arXiv   pre-print
To address these problems, we propose a conditional generative model, named 3DLinker, which is able to predict anchor atoms and jointly generate linker graphs and their 3D structures based on an E(3) equivariant  ...  Deep learning has achieved tremendous success in designing novel chemical compounds with desirable pharmaceutical properties.  ...  The linker design problem should be extended to include the 3D information, and a 3D-aware generative model is in need for the generation of realistic linkers, rather than invoke a graph generative model  ... 
arXiv:2205.07309v1 fatcat:ofrkitukljf3tng5q4nlhcaxy4

SyntaLinker: Automatic Fragment Linking with Deep Conditional Transformer Neural Networks

Yuyao Yang, Shuangjia Zheng, Shimin Su, Chao Zhao, Jun Xu, Hongming Chen
2020 Chemical Science  
Linking fragments to generate a focused compound library for a specific drug target is one of the challenges in fragment-based drug design (FBDD). Hereby, we propose a new program named...  ...  [32] [33] [34] The deep generative models have been applied in de novo molecular design [35] [36] [37] [38] and lead optimization.  ...  Recently, advances in the development of deep generative models have spawned a mass of promising methods to address the structure generation issue in drug design.  ... 
doi:10.1039/d0sc03126g pmid:34123096 pmcid:PMC8163338 fatcat:ontsqijhtreqrjjfyqil2xuqmm

In Silico Designing of a Novel Antibody Conjugate as a Potential Immunotherapeutic for the Treatment of CD19-Positive Hematologic Malignancies

Pooria Safarzadeh Kozani
2021 Trends in Medical Sciences  
Methods: Four different linker peptides were used for the conjugation of HuFMC63 to GrB, and the 3D structure of these antibody conjugates were predicted using GalaxyWEB.  ...  Objectives: This study aimed to design an antibody conjugate through the recombinant conjugation of a humanized CD19-specific single-chain variable fragment (scFv), named HuFMC63, to granzyme B (GrB) using  ...  This demonstrates that minor structural improvements were made to the 3D model of Hu63-(G4S)3-GrB to relieve the unfavorable clashes. This 3D model was used for the further steps.  ... 
doi:10.5812/tms.117219 fatcat:asmkypqzmje4rgpmbnpfyjcs54

REST: A method for restoring signals and revealing individual macromolecule states in cryo-ET [article]

Haonan Zhang, Yan Li, Yanan Liu, Dongyu Li, Lin Wang, Kai Song, Keyan Bao, Ping Zhu
2022 bioRxiv   pre-print
AbstractCryo-electron tomography (cryo-ET) is widely used to explore the 3D density of biomacromolecules.  ...  However, the heavy noise and missing wedge effect prevent directly visualizing and analyzing the 3D reconstructions.  ...  We would like to thank Jianguo Zhang, Xing Jia, Xiaojun Huang, Boling Zhu, for their technical help and support with electron microscopy.  ... 
doi:10.1101/2022.07.11.499538 fatcat:7jj7bsu635fthlyh457bs3utue

Application advances of deep learning methods for de novo drug design and molecular dynamics simulation

Qifeng Bai, Shuo Liu, Yanan Tian, Tingyang Xu, Antonio Jesús Banegas‐Luna, Horacio Pérez‐Sánchez, Junzhou Huang, Huanxiang Liu, Xiaojun Yao
2021 Wiley Interdisciplinary Reviews. Computational Molecular Science  
The application progress of deep learning is also summarized for MD simulations. Furthermore, IML is introduced for the deep learning model interpretability of de novo drug design and MD simulations.  ...  Our paper deals with an interesting topic about deep learning applications of de novo drug design and MD simulations for the scientific community.  ...  JR202004)" who provided the grant for this manuscript.  ... 
doi:10.1002/wcms.1581 fatcat:lzwgw6oigbaspcvxuetancbthy

Molecular Simulation and Activity Studies of Oxametacin as an HDAC Inhibitor

Fanbo Jing, Lei Zhang, Yepeng Luan, Jiang Bian
2017 Letters in Drug Design & Discovery  
In-vitro inhibition activity screening and in-silico 3D molecular modeling approaches are important tools for design and development of specific histone deacetylase (HDAC) inhibitors.  ...  This study demonstrated that there is no sole gold standard technique for inhibitor design, and it was concluded that a combination of molecular modeling and activity screening assays will ensure more  ...  Sevim Dalkara from Hacettepe University's Faculty of Pharmacy for providing the compounds for this study.  ... 
doi:10.2174/1570180814666170505123930 fatcat:4eajr5nztvgofkwsjonjujr3rq

Bio nano ink for 4D printing membrane proteins

Anu Stella Mathews, Sinoj Abraham, Surjith Kumar Kumaran, Jiaxin Fan, Carlo Montemagno
2017 RSC Advances  
Photo curable bio-nano ink was designed, developed and printed using a stereolithographic printer.  ...  Matthew Christensen for preparing bR and Sumalee Salahub for FE-SEM operations.  ...  Acknowledgements The authors thank Alberta Innovates Technology Futures (AITF) iCORE chair funding, National Institute of Nano Technology (NINT) Facilities and Antonio Jiménez for synthesizing peptide,  ... 
doi:10.1039/c7ra07650a fatcat:sx2jecu3uvb25cclzm356ljevu

Designing a Novel Multi-Epitope Vaccine against SARS-CoV-2; Implication for Viral Binds and Fusion Inhibition through Inducing Neutralizing Antibodies [article]

Seyed Amir Hossein Mohammadzadeh Hosseini Moghri, Mojtaba Ranjbar, Hadi Hassannia, Fatemeh Khakdan
2021 bioRxiv   pre-print
In the present study, several immunoinformatics tools are used for analyzing the spike (S) glycoprotein sequence including the prediction of the potential linear B-cell epitopes, B-cell multi-epitope design  ...  In this regard, the RBD and spike cleavage site is the most probable target for vaccine development to inducing binds and fusion inhibitors neutralizing antibodies.  ...  I-TASSER generated 3D-model was used to represent the RBD residues of trimeric spike 122 (S) glycoprotein ( Figure 1A ) based on the surface exposed and S-ACE2 ( Figure 1B) 126 .  ... 
doi:10.1101/2021.06.16.448772 fatcat:73pe4j4lmrfr7ffxleq5fdfnhm

Search for the pharmacophore of histone deacetylase inhibitors using pharmacophore query and docking study

Atefeh Haji Agha Bozorgi, Afshin Zarghi
2014 Iranian journal of pharmaceutical research  
Creating pharmacophor models in order to design new molecules or search a library for finding lead compounds is of great interest.  ...  With the aid of this pharmacophore model and docking result, 3D searches in large databases can be performed, leading to a significant enrichment of active analogs.  ...  Hydrophobic linker, which is inserted into the narrow 11A˚deep hydrophobic channel which leads to the active site, generated by Phenylalanine, Histidine, Glycin, Methionin and Tyrosine.There is a 14A ˚  ... 
pmid:25587304 pmcid:PMC4232781 fatcat:n4z6c5rfzbardbdk344ayfusoq

Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2

Muhammad Tahir Ul Qamar, Farah Shahid, Sadia Aslam, Usman Ali Ashfaq, Sidra Aslam, Israr Fatima, Muhammad Mazhar Fareed, Ali Zohaib, Ling-Ling Chen
2020 Infectious Diseases of Poverty  
Taken together, 276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes (CTL), 6 helper T lymphocyte (HTL) and 4 B-cell epitopes with suitable adjuvant and linkers.  ...  The MESV developed in this study is capable of generating immune response against COVID-19.  ...  Acknowledgements Authors would like to acknowledge Guangxi University and Government College University Faisalabad for providing facilities for this study.  ... 
doi:10.1186/s40249-020-00752-w pmid:32938504 pmcid:PMC7492789 fatcat:gx3dxjjpwvamjg7bjub2njw2ga

Design of a Multi-Epitopes Vaccine against Hantaviruses: An Immunoinformatics and Molecular Modelling Approach

Saba Ismail, Sumra Wajid Abbasi, Maha Yousaf, Sajjad Ahmad, Khalid Muhammad, Yasir Waheed
2022 Vaccines  
The designed vaccine structures were modelled and subjected to error refinement and disulphide engineering to enhance their stability.  ...  The designed vaccine was then joined to three different adjuvants—TLR4-agonist adjuvant, β-defensin, and 50S ribosomal protein L7/L12—using an EAAAK linker to boost up immune-stimulating responses and  ...  To create a more stable vaccine design, a GPGPG linker was inserted between the epitope sequences.  ... 
doi:10.3390/vaccines10030378 pmid:35335010 pmcid:PMC8953224 fatcat:c3asf4czuzfrjhx2jaaiwuzjma

Bis-isoquinolinium and bis-pyridinium acetylcholinesterase inhibitors: in vitro screening of probes for novel selective insecticides

Veronika Hrabcova, Jan Korabecny, Brigita Manyova, Lenka Matouskova, Tomas Kucera, Rafael Dolezal, Kamil Musilek, Lukas Gorecki, Eugenie Nepovimova, Kamil Kuca, Daniel Jun
2017 RSC Advances  
Library screening of pyridinium-based compounds, acting as acetylcholinesterase inhibitors, for their potential insecticidal efficacy.  ...  Acknowledgements The authors would like to thank Jitka Turanova for her technical assistance.  ...  model (PDB ID: 2HCP).  ... 
doi:10.1039/c7ra05838a fatcat:lbol5mivnvgexeinx7gflz7gj4

Protein sequence-to-structure learning: Is this the end(-to-end revolution)? [article]

Elodie Laine, Stephan Eismann, Arne Elofsson, Sergei Grudinin
2021 arXiv   pre-print
architectures, i.e. differentiable models starting from a sequence and returning a 3D structure.  ...  The potential of deep learning has been recognized in the protein structure prediction community for some time, and became indisputable after CASP13.  ...  The founder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.  ... 
arXiv:2105.07407v2 fatcat:6szubg7q2rajlj3l4vyzqri3nm
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