I've updated the covalent inhibitors page to include details of two covalent fragment libraries that have been used in fragment screening.
A new initiative that should be very useful,
An event (with free registration) to foster the In silico Toxicology Community in the UK and beyond. Scientific contributions are as welcome as those on ongoing work, regulatory aspects, industry perspectives, databases, relevant software, journals etc. in the field. This event is meant to stimulate interactions and discussions, hence speakers are asked to present both about in silico toxicology approaches that are already useful to be applied at the current stage, as well as aspects that don't work that well right now, and where future developments are hence needed.
Venue 26 November 2019, Unilever Lecture Theatre, Department of Chemistry, University of Cambridge (CB2 1EW)
Full details and link for registration here In Silico Toxicology' Network Meeting 2019.
A small update to the Ester and Amide bioisosteres page.
Just checking the half-year viewing stats for the Drug Discovery Resources section of the website.
The Drug Discovery Resources pages are intended to act as a resource for scientists undertaking drug discovery, they were initially based on a course I give but have been expanded to give much more detail and to cover subjects not covered in the course.
Over the first six months there were nearly 35,000 users with users on average viewing 2-3 pages. The visitors come from 152 different countries with the US (33%), UK (14%) , India (8%), Germany (3.2%) and Canada (3.1%) topping the list.
The most viewed pages over this period were
- Calculating Physicochemical Properties
- Distribution and Plasma Protein Binding
- Molecular Interactions
- Kinase Inhibitors
- Acid Bioisosteres
- Aromatic Bioisosteres
- Solvation and desolvation
- Aspartic Acid Proteases
- CYP Interactions
- Fragment based screening
Looking at the operating systems 56% are Windows users, 20% Mac users, 10% iOS and 10% Android, Chrome dominates the browser stats (65%) with Safari second (17%) and Firefox third (10%).
I just got news of the first public release of CO-ADD screening data
CO-ADD is a non-for-profit initiative led by academics at The University of Queensland. Our goal is to screen compound for antimicrobial activity for academic research groups and generate a public knowledge database for the development of novel agents for the treatment of microbial infections. The knowledge base contains chemical structures and antimicrobial activity data from CO-ADD’s screening, made publicly available by the academic research groups, with more data to be released over time.
Studies of hydrogen bond strength and directionality are largely based on crystal structures which can be biased by crystal packing forces. In a systematic QM study of a wide range of hydrogen bonding groups by Diogo Santos-Martins, Stefano Forli, 34 donors and 67 acceptors DOI they showed there is no correlation between the strength of the hydrogen bond and directionality.
Results demonstrate that there are very strong HB acceptors (e.g.,DMSO) with nearly isotropic interactions, and weak ones (e.g.,thioacetone) with a sharp directional profile. Similarly, groups can have comparable directional propensity, but be very distant in the strength spectrum (e.g., thioacetone and pyridine).
This work also includes a fabulous sheet in the supplementary information giving details of interaction energies for various groups.
I've updated the molecular interactions page.
The GHIT Fund announces an investment opportunity for the Target Research Platform
The GHIT Fund announces an investment opportunity for the Target Research Platform (TRP) in Partnership with the Wellcome Trust. The TRP investments are intentionally broad in potential scope and focus on new technologies and novel approaches.
TRP investments are intentionally broad in potential scope and focus on new technologies and novel approaches. Proposals must be within the project scope and investment eligibility below in order to be considered. The TRP is currently focused on technologies and approaches that address unmet or priority needs within malaria, tuberculosis, HIV/AIDS and Neglected Tropical Diseases listed in the GHIT Intent to Apply form.
MRC/AstraZeneca Centre for Lead Discovery
The MRC/AstraZeneca Centre for Lead Discovery (CLD) aims to support academic researchers in discovering potential starting points for small molecule therapeutic approaches with a clear line-of-sight to therapeutic use. The MRC/AZ Centre for Lead Discovery will form a unique cornerstone for academic and industrial drug discovery projects by supplying high throughput screening (HTS) infrastructure (NiCoLA-B).
Canada-UK Artificial Intelligence Initiative
The call aims to support innovative and cutting-edge interdisciplinary AI research that encourages the exploration of new interdisciplinary research methodologies, approaches and tools that cuts across at least two of the following research domains:
- social sciences and humanities;
- health and biomedical sciences; and
- natural sciences and engineering (including computational and/or mathematical sciences).
There is also a more comprehensive listing of grant funding here.
I was going to highlight this article a while back "Academia and industry: allocating credit for discovery and development of new therapies" DOI but got distracted. However I notice that Derek Lowe has written a commentary that is far more detailed than I could have written on his In the Pipeline Blog.
You can read it here Where Drugs Come From it is well worth spending a little reading, digesting and then sending the link to others.
cansar black v1.1.1 now available - includes improved search, new protein family page, and performance improvements
canSAR is an integrated knowledge-base that brings together multidisciplinary data across biology, chemistry, pharmacology, structural biology, cellular networks and clinical annotations, and applies machine learning approaches to provide drug-discovery useful predictions. canSAR’s goal is to enable cancer translational research and drug discovery through providing this knowledge to researchers from across different disciplines. It provides a single information portal to answer complex multi-disciplinary questions including - among many others: what is known about a protein, in which cancers is it expressed or mutated and what chemical tools and cell line models can be used to experimentally probe its activity? What is known about a drug, its cellular sensitivity profile and what proteins is it known to bind that may explain unusual bioactivity?
The latest update of the Open Targets Platform, release 19.06 is available.
This update includes
Target safety information
As a follow-up to the safety data in Open Targets Platform release 19.04, now has more targets with known safety effects and safety risk information, including TBXA2R and JAK2.
TEPs and chemical probes
In this release, they've included the latest Target Enabling Packages (TEPs) for GALT, GALK1 and MLLT1. Also added more chemical probes, small-molecule modulators of a protein’s function that can be used in cell-based or animal studies.
A new release always means new evidence available for novel target-disease associations.