scholarly journals State of the Art in African Trypanosome Drug Discovery

2011 ◽  
Vol 11 (10) ◽  
pp. 1255-1274 ◽  
Author(s):  
Robert T. Jacobs ◽  
Bakela Nare ◽  
Margaret A. Phillips
2020 ◽  
Author(s):  
Yuyao Yang ◽  
Shuangjia Zheng ◽  
Shimin Su ◽  
Jun Xu ◽  
Hongming Chen

Fragment based drug design represents a promising drug discovery paradigm complimentary to the traditional HTS based lead generation strategy. How to link fragment structures to increase compound affinity is remaining a challenge task in this paradigm. Hereby a novel deep generative model (AutoLinker) for linking fragments is developed with the potential for applying in the fragment-based lead generation scenario. The state-of-the-art transformer architecture was employed to learn the linker grammar and generate novel linker. Our results show that, given starting fragments and user customized linker constraints, our AutoLinker model can design abundant drug-like molecules fulfilling these constraints and its performance was superior to other reference models. Moreover, several examples were showcased that AutoLinker can be useful tools for carrying out drug design tasks such as fragment linking, lead optimization and scaffold hopping.


2019 ◽  
Author(s):  
Wengong Jin ◽  
Regina Barzilay ◽  
Tommi S Jaakkola

The problem of accelerating drug discovery relies heavily on automatic tools to optimize precursor molecules to afford them with better biochemical properties. Our work in this paper substantially extends prior state-of-the-art on graph-to-graph translation methods for molecular optimization. In particular, we realize coherent multi-resolution representations by interweaving trees over substructures with the atom-level encoding of the original molecular graph. Moreover, our graph decoder is fully autoregressive, and interleaves each step of adding a new substructure with the process of resolving its connectivity to the emerging molecule. We evaluate our model on multiple molecular optimization tasks and show that our model outperforms previous state-of-the-art baselines by a large margin.


2011 ◽  
Vol 999 (999) ◽  
pp. 1-29
Author(s):  
Jeremy N. Burrows ◽  
Kelly Chibale ◽  
Timothy N.C. Wells

2021 ◽  
Vol 15 (8) ◽  
pp. 898-911
Author(s):  
Yongqing Zhang ◽  
Jianrong Yan ◽  
Siyu Chen ◽  
Meiqin Gong ◽  
Dongrui Gao ◽  
...  

Rapid advances in biological research over recent years have significantly enriched biological and medical data resources. Deep learning-based techniques have been successfully utilized to process data in this field, and they have exhibited state-of-the-art performances even on high-dimensional, nonstructural, and black-box biological data. The aim of the current study is to provide an overview of the deep learning-based techniques used in biology and medicine and their state-of-the-art applications. In particular, we introduce the fundamentals of deep learning and then review the success of applying such methods to bioinformatics, biomedical imaging, biomedicine, and drug discovery. We also discuss the challenges and limitations of this field, and outline possible directions for further research.


2021 ◽  
Vol 35 (08) ◽  
pp. 2130002
Author(s):  
Connor J. Morris ◽  
Dennis Della Corte

Molecular docking and molecular dynamics (MD) are powerful tools used to investigate protein-ligand interactions. Molecular docking programs predict the binding pose and affinity of a protein-ligand complex, while MD can be used to incorporate flexibility into docking calculations and gain further information on the kinetics and stability of the protein-ligand bond. This review covers state-of-the-art methods of using molecular docking and MD to explore protein-ligand interactions, with emphasis on application to drug discovery. We also call for further research on combining common molecular docking and MD methods.


2019 ◽  
Vol 20 (3) ◽  
pp. 185-193 ◽  
Author(s):  
Natalie Stephenson ◽  
Emily Shane ◽  
Jessica Chase ◽  
Jason Rowland ◽  
David Ries ◽  
...  

Background:Drug discovery, which is the process of discovering new candidate medications, is very important for pharmaceutical industries. At its current stage, discovering new drugs is still a very expensive and time-consuming process, requiring Phases I, II and III for clinical trials. Recently, machine learning techniques in Artificial Intelligence (AI), especially the deep learning techniques which allow a computational model to generate multiple layers, have been widely applied and achieved state-of-the-art performance in different fields, such as speech recognition, image classification, bioinformatics, etc. One very important application of these AI techniques is in the field of drug discovery.Methods:We did a large-scale literature search on existing scientific websites (e.g, ScienceDirect, Arxiv) and startup companies to understand current status of machine learning techniques in drug discovery.Results:Our experiments demonstrated that there are different patterns in machine learning fields and drug discovery fields. For example, keywords like prediction, brain, discovery, and treatment are usually in drug discovery fields. Also, the total number of papers published in drug discovery fields with machine learning techniques is increasing every year.Conclusion:The main focus of this survey is to understand the current status of machine learning techniques in the drug discovery field within both academic and industrial settings, and discuss its potential future applications. Several interesting patterns for machine learning techniques in drug discovery fields are discussed in this survey.


2011 ◽  
Vol 11 (10) ◽  
pp. 1226-1254 ◽  
Author(s):  
Jeremy N. Burrows ◽  
Kelly Chibale ◽  
Timothy N.C. Wells

2001 ◽  
Vol 7 (S2) ◽  
pp. 622-623
Author(s):  
Xiaoyou Ying ◽  
Jean Sprinkle Cavallo ◽  
Bruce McCullough

Digital microscopy, the integration of digital and microscopy technologies, was initiated for quantitative microscopic image analysis, but it is now for almost all microscopy applications. During the past decade, with the advance of digital technologies, digital microscopy imaging is becoming an indispensable technology in drug discovery.We started establishing state-of-the-art digital microscopy imaging for drug discovery with the investigation of bioimaging applications at our US research site. Our results shown that all the top 5 bioimaging needs require computer-aided microscopy. Based on this investigation and our review of the microscopy imaging applications in the pharmaceutical industry, we determined four directions for microscopy in drug discovery: multidimensional/multimodal microscopy, digitalization, automation, and bioimage informatics.Multidimensional/multimodal microscopy imaging is required by the nature of biological research, which is fundamental in drug discovery. From genomic imaging to pathology observation, we require biological details and compound activities at the levels from subcellular organelles to organ tissues, from cellular signaling to anatomical locations of compounds.


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