[ccp4bb] CCPBioSim Industry Talk - 10 July

[Sarah Fegan - STFC UKRI]

Dear all,



Registration is now open for our next industry talk on 10 July 2024 at 2pm UK 
time. The talk by Steve Maginn, Chemical Computing Group / Molecular Graphics 
and Modelling Society, has the title "At the Interface of Academia and Industry 
for 35 Years... (aka - "You get less time for murder!")". Details and the free 
registration link can be found at https://www.ccpbiosim.ac.uk/chemcompgroup2024.



Abstract: I graduated with a PhD in chemistry from the University of Liverpool 
in 1989 and went straight into a research job in industry in a company that was 
then an international household name, ICI. At that time, such a role was 
considered something akin to a "job for life" - but things very soon changed. 
During the last 35 years I have spent my career working in science at the 
border between industry and academia, in a variety of both formal and informal 
roles, initially in research but moving gradually towards more commercial and 
organisational tasks in which my scientific background proved to be a strong 
asset. During this presentation, I will describe those roles and the reasoning 
behind the decisions that led to my taking them on, highlighting what I 
believe, despite ever-changing economic conditions and pressures, are the keys 
to a successful career in science; adaptability and networking.



Best wishes,

Sarah



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[ccp4bb] CCPBioSim Industry talk - MDAnalysis 19 June

[Sarah Fegan - STFC UKRI]

Hi all,
Our next online Industry Talk is by Richard Gowers, a core developer of 
MDAnalysis. The talk will take place on Wednesday 19 June 2024 at 2pm UK time. 
Free registration can be found at https://www.ccpbiosim.ac.uk/mda-talk2024.
Title: MDAnalysis and Alchemical Simulations
Abstract: MDAnalysis is a popular Python package for the analysis of molecular 
dynamics simulation data.  After introducing the package in broad strokes, this 
talk will give insight into how this package has been used and extended to 
process data coming from so-called "alchemical simulations"; where molecules 
are perturbed through non-physical states to provide estimates of properties 
such as binding affinities.  Topics included will be biopolymer recognition, 
handling of multistate simulation data and analysing hybrid topology alchemical 
models.
Best wishes,
Sarah



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[ccp4bb] CCPBioSim Industry Talk - D E Shaw 29 May

[Sarah Fegan - STFC UKRI]

Dear all,



This online talk is by Brannon Batson who is a hardware design engineer at D. 
E. Shaw Research. The talk takes place on Wednesday 29 May 2024 at 15:00 UK 
time. To register visit https://www.ccpbiosim.ac.uk/deshaw2024.



Title: Using specialized hardware pipelines to massively accelerate molecular 
dynamics simulations in Anton 3



Abstract: At D. E. Shaw Research, we have designed and built multiple 
generations of highly successful special-purpose supercomputers for molecular 
dynamics simulations.  The newest generation, Anton 3, achieves simulation 
speeds at least 100-fold faster than any other currently available 
supercomputer on a wide range of biomolecular systems.  Anton machines are an 
essential foundational technology for our scientific and drug discovery 
efforts.  This talk will describe how we co-design hardware, software, and 
algorithms to accelerate both research and drug discovery, focusing on how 
specialized hardware pipelines contribute to the enormous speedups that Anton 
machines achieve.



Best wishes,

Sarah



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[ccp4bb] CCPBioSim Industry Talk - Schrodinger 17 April 2024

[Sarah Fegan - STFC UKRI]

Hi all,

Free registration is open for our upcoming online Industry Talk by Márton Vass 
from Schrödinger at 14:00 British Summer Time on 17 April 2024. Details and 
registration link can be found at https://www.ccpbiosim.ac.uk/schrodinger2024.

Title: Structure-based target enablement with IFD-MD and FEP+

Abstract: AlphaFold2 and other recently developed machine learning protein 
structure prediction tools have sparked a new interest in enabling 
structure-based drug discovery for targets with no available relevant 
structural information. At Schrödinger, we are working towards understanding 
the possible uses and limitations of ML predicted structures and methods of 
refining them for accurate physics-based modelling.

We have previously shown that raw AlphaFold2 structures can provide virtual 
screening enrichments on a par with those achieved using apo protein structures 
and that this performance can be improved to similar levels seen with relevant 
holo structures using tools like Induced Fit Docking with Molecular Dynamics 
(IFD-MD).

The use of AlphaFold2 models can be extended further to ligand optimisation by 
combining IFD-MD refinement with FEP+, to derive models that are capable of 
recapitulating known SAR and which, subsequently, can be used for prospective 
free-energy calculations.

In addition to its use in on-target modelling, we've extended the use of IFD-MD 
to off-target modelling, where the use of a new and faster 'consensus IFD-MD' 
approach allows us to run the workflow on a larger number of input protein 
conformations. This method appears to show promise for enabling structure-based 
ADMET modelling by targeting commonly encountered off-targets, such as CYPs, 
PXR and hERG.



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[ccp4bb] CCPBioSim Industry Talk - Sosei Heptares - 27 March 2024

[Sarah Fegan - STFC UKRI]

Dear all,

Our next online industry talk is by Brian Bender of Sosei Heptares on 27 March 
2024 at 14:00 UK time. Registration is free but required. Details and 
registration can be found at https://www.ccpbiosim.ac.uk/soseiheptares2024.

Title: "Applications of AlphaFold and Generative Molecular Design for GPCR SBDD"

Abstract: Methodologies for structure prediction and molecule design are 
advancing at a rapid pace. Staying on top of recent developments requires 
testing them to understand if they are truly useful for prospective research. 
In this talk, we will explore the uses of AlphaFold and generative molecular 
design in the context of drug discovery at a class of membrane proteins known 
as G protein-coupled receptors. Through the use of retrospective studies, we 
demonstrate the possibilities and limitations of these technologies. For the 
limitations that do exist, we will show how we and others in the field are 
working to overcome these challenges. Both AlphaFold and generative molecular 
design are powerful methods but require attention to detail to be useful in 
active drug discovery programs.

Please feel free to share this with anyone who might be interested.

Best wishes,
Sarah



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[ccp4bb] CCPBioSim Industry Talk - Kuano AI

[Sarah Fegan - STFC UKRI]

Dear all,

Happy New Year! Our first Industry Talk of 2024 will be at 2pm UK time on 24 
January by David Wright of KuanoAI. Details and free registration can be found 
at https://www.ccpbiosim.ac.uk/kuano2024.

Title: Quantum Leaps in Drug Discovery: The Journey of Our Startup

Speaker: David Wright, KuanoAI

Abstract: Kuano is a drug design startup I (David Wright, reformed Fortran 
coder and former UCL post doc) co-founded in the first UK lockdown in 2020 with 
the goal of creating better therapeutics with a combination of quantum 
simulation and AI. Despite the high rate of early biotech startup failures we 
are still here 4 years later and looking good to achieve further funding next 
year. In this talk, I will explain how I transitioned from academia to creating 
a company and managing a highly multidisciplinary team that spans medicinal 
chemistry to quantum computing. Along the way I will explain some of the 
science behind Kuano's drug design platform and also showcase some of our 
projects and achievements.

Please feel free to share.

Best wishes,
Sarah



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[ccp4bb] CCPBioSim Industry Talk - 29 November 2023

[Sarah Fegan - STFC UKRI]

Hi All,

The next Industry Talk will be "Hydrogen bond donor-acceptor asymmetries in 
drug design" given by Peter Kenny (retired) on 29 November 2023 at 2 pm UK 
time. Details and free registration link can be found at 
https://www.ccpbiosim.ac.uk/hydrogenbond2023.

Abstract: The presentation will highlight the importance of polarity in drug 
design and show how alkane/water logP measurements can be used to estimate 
polarity for individual HBAs and HBDs. In molecular structures of interest to 
drug designers, HBAs are typically more polar and more numerous than HBDs and 
these HBD-HBA 'asymmetries' are relevant when optimizing aqueous solubility and 
membrane permeability. The presence of an HBD in a molecular structure 
generally implies that an HBA is also present (but not vice versa) and this is 
relevant when optimizing interactions between targets and ligands. The 
presentation will conclude by considering the design implications of 
'frustrated' hydration.

Please feel free to share this with anyone who might be interested.

Best wishes,
Sarah



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[ccp4bb] CCPBioSim Industry Talk Atommap

[Sarah Fegan - STFC UKRI]

Hi all,

Our next online industry talk will be given by Huafeng Xu of Atommap (see title 
and abstract below) on Wednesday 26 July 2023 at 3:30 pm UK time. Registration 
is free, but required to get the Zoom link. Details and link to registration 
can be found at 
www.ccpbiosim.ac.uk/atommap2023.

Best wishes,
Sarah

Title: Computation-driven drug discovery

Abstract: We are witnessing a rapid rise of computation in the drug discovery 
industry.  The renewed excitement about computational modeling is attributable 
to the dramatic growth of computing power and substantial and continuous 
improvements in the models of computational chemistry and biology, including 
both progress in mature physics-based models and the emergence of deep neural 
network (DNN) and other machine learning models.  Here, I illustrate the use of 
multi-scale, multi-fidelity molecular modeling in computation-driven drug 
discovery, focusing on exploiting the conformational dynamics in biomolecules 
to enable new therapeutic opportunities.  By incorporating biophysical data, 
such as hydrogen-deuterium exchange (HDX) and nuclear magnetic resonance (NMR), 
into molecular dynamics simulations (augmented by enhanced sampling 
techniques), we turn the low-resolution experimental measurements into accurate 
models of structural ensembles of proteins at atomistic resolution, yielding 
novel structural hypotheses for drug design.  Using this approach, we have 
optimized a small molecule agonist for both affinity and stabilization of the 
active conformation of Stimulator of Interferon Genes (STING) and rapidly 
advanced the program into clinical trial, and we have designed an active 
targeted protein degrader of SMARCA2 based on a modeled conformation of the 
SMARCA2-degrader-VHL ternary complex previously unobserved but subsequently 
confirmed in crystallography.  I discuss the path to general application of 
computation-driven drug discovery.



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[ccp4bb] CCPBioSim Industry Talk - online

[Sarah Fegan - STFC UKRI]

Hi all,

Our next industry talk is coming up soon - Wednesday 28 June 2023 at 2pm UK 
time. This online talk by Antonija Kuzmanic from Schrodinger will cover 
protein-ligand structures and drug design along with her experiences developing 
a career in industry. Please visit https://www.ccpbiosim.ac.uk/schrodinger2023 
for all the details and to register for a Zoom link.

Title: Application of molecular dynamics simulations in predicting and 
analysing protein-ligand interactions

Abstract: Many structure-based drug design (SBDD) methods, including advanced 
free energy calculations, require accurate, atomic-level detail of the target 
protein structure in complex with a member of the ligand series of interest to 
perform optimally. Consequently, the domain of applicability of SBDD is limited 
by the availability of high-resolution crystal structures of the target protein 
or its close homologues. Alternatively, low-resolution structures could also be 
of use, but they might need refining, while AlphaFold2 structures completely 
lack a bound ligand, so the subtle details of protein-ligand interactions are 
left undetermined. In this talk, I will discuss simulation-based approaches 
that allow us to elucidate the intricacies of the protein-ligand interactions 
with a focus on a recently developed workflow (IFD-MD) that can predict the 
atomic details of the protein-ligand complex structure needed for SBDD, 
starting from either the target with a different ligand in the binding site or 
from a structure of a highly homologous protein.

Best wishes,
Sarah



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[ccp4bb] CCPBioSim Industry Talk - Rescheduled

[Sarah Fegan - STFC UKRI]

Dear all,

The Industry Talk has been rescheduled, it will now be on Wednesday 26 April 
2023 at 3 pm UK time. If you had already registered, your registration will 
still be valid for the new date. The speaker is Alexander D. MacKerell and the 
title is "Introduction to Site Identification by Ligand Competitive Saturation 
(SILCS) and its Application in Drug Design and Development." Details and 
registration at https://www.ccpbiosim.ac.uk/silcs2023.

Abstract: SILCS involves generating a pre-computed ensemble of 1) the 
distribution of solutes and water in the full 3D space of proteins or RNA as 
well as 2) the conformations of the macromolecule using combined oscillating 
excess chemical potential Grand-Canonical Monte Carlo/Molecular Dynamics 
simulations. From the precomputed ensemble 3D "FragMaps" are produced that 
represent functional group free energies relative to aqueous solution in the 
full 3D space of the macromolecular system.  The free energies include 
contributions on macromolecular flexibility, desolvation of the functional 
groups and the macromolecule and functional group-macromolecular interactions.  
Once precomputed the SILCS FragMaps may be used for a variety of free energy 
related calculations in a highly computationally accessible manner.  These 
include binding affinities of fragments and drug-like molecules, generation of 
pharmacophores, and lead compound optimization. In addition, FragMaps may be 
utilized for calculation of protein-protein interactions, glycan-protein 
interactions, and the full distributions of ligands in the 3D space of 
macromolecules for use in allosteric binding site identification, 
fragment-based drug design, and the rational design of excipients for biologics 
drugs formulation.  In addition, the SILCS methodology may be applied to 
membranes allowing for investigations of the partitioning of molecules in 
interfacial systems and prediction of permeabilities in conjunction with 
artificial intelligence.  An introduction to the SILCS technology and details 
of various applications will be presented.

Best wishes,
Sarah



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Re: [ccp4bb] CCPBioSim Industry Talk

[Dina Hussein]

> On Feb 17, 2023, at 11:38 AM, Sarah Fegan - STFC UKRI 
> <711df86179e2-dmarc-requ...@jiscmail.ac.uk> wrote:
> 
> 
> Dear all,
>  
> We are pleased to announce another Industry Talk. This talk will be on 
> Wednesday 19 April 2023 at 3 pm UK time. The speaker is Alexander D. 
> MacKerell and the title is “Introduction to Site Identification by Ligand 
> Competitive Saturation (SILCS) and its Application in Drug Design and 
> Development.” Details and registration at 
> https://www.ccpbiosim.ac.uk/silcs2023.
>  
> Abstract: SILCS involves generating a pre-computed ensemble of 1) the 
> distribution of solutes and water in the full 3D space of proteins or RNA as 
> well as 2) the conformations of the macromolecule using combined oscillating 
> excess chemical potential Grand-Canonical Monte Carlo/Molecular Dynamics 
> simulations. From the precomputed ensemble 3D “FragMaps” are produced that 
> represent functional group free energies relative to aqueous solution in the 
> full 3D space of the macromolecular system.  The free energies include 
> contributions on macromolecular flexibility, desolvation of the functional 
> groups and the macromolecule and functional group-macromolecular 
> interactions.  Once precomputed the SILCS FragMaps may be used for a variety 
> of free energy related calculations in a highly computationally accessible 
> manner.  These include binding affinities of fragments and drug-like 
> molecules, generation of pharmacophores, and lead compound optimization. In 
> addition, FragMaps may be utilized for calculation of protein-protein 
> interactions, glycan-protein interactions, and the full distributions of 
> ligands in the 3D space of macromolecules for use in allosteric binding site 
> identification, fragment-based drug design, and the rational design of 
> excipients for biologics drugs formulation.  In addition, the SILCS 
> methodology may be applied to membranes allowing for investigations of the 
> partitioning of molecules in interfacial systems and prediction of 
> permeabilities in conjunction with artificial intelligence.  An introduction 
> to the SILCS technology and details of various applications will be presented.
>  
> Best wishes,
> Sarah
> 
> To unsubscribe from the CCP4BB list, click the following link:
> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1



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[ccp4bb] CCPBioSim Industry Talk

[Sarah Fegan - STFC UKRI]

Dear all,

We are pleased to announce another Industry Talk. This talk will be on 
Wednesday 19 April 2023 at 3 pm UK time. The speaker is Alexander D. MacKerell 
and the title is "Introduction to Site Identification by Ligand Competitive 
Saturation (SILCS) and its Application in Drug Design and Development." Details 
and registration at https://www.ccpbiosim.ac.uk/silcs2023.

Abstract: SILCS involves generating a pre-computed ensemble of 1) the 
distribution of solutes and water in the full 3D space of proteins or RNA as 
well as 2) the conformations of the macromolecule using combined oscillating 
excess chemical potential Grand-Canonical Monte Carlo/Molecular Dynamics 
simulations. From the precomputed ensemble 3D "FragMaps" are produced that 
represent functional group free energies relative to aqueous solution in the 
full 3D space of the macromolecular system.  The free energies include 
contributions on macromolecular flexibility, desolvation of the functional 
groups and the macromolecule and functional group-macromolecular interactions.  
Once precomputed the SILCS FragMaps may be used for a variety of free energy 
related calculations in a highly computationally accessible manner.  These 
include binding affinities of fragments and drug-like molecules, generation of 
pharmacophores, and lead compound optimization. In addition, FragMaps may be 
utilized for calculation of protein-protein interactions, glycan-protein 
interactions, and the full distributions of ligands in the 3D space of 
macromolecules for use in allosteric binding site identification, 
fragment-based drug design, and the rational design of excipients for biologics 
drugs formulation.  In addition, the SILCS methodology may be applied to 
membranes allowing for investigations of the partitioning of molecules in 
interfacial systems and prediction of permeabilities in conjunction with 
artificial intelligence.  An introduction to the SILCS technology and details 
of various applications will be presented.

Best wishes,
Sarah



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[ccp4bb] CCPBioSim Industry Talk

[Sarah Fegan - STFC UKRI]

Dear all,

We are very excited to be hosting Julien Michel for his Industry Talk 
presentation on the 8th March 2023 at 2pm:

"Promoting open collaboration in computer-aided drug design with the OpenBioSim 
Community Interest Company".

You can register for the seminar below:
https://www.ccpbiosim.ac.uk/openbiosim2023

And here is Julien's abstract:
Abstract
OpenBioSim (OBS) is a not-for-profit company that aims to promote and sustain 
the use of open-source chemical research software in academia and industry. OBS 
works with industry partners to integrate open-source software as components of 
technology platforms, and to provide long term support for open-source projects 
that have demonstrated scientific utility.
This webinar will discuss the motivations for setting up OpenBioSim, and 
highlight the work OpenBioSim is currently doing with the open-source projects 
Sire and BioSimSpace to support industrial applications in the domain of 
computer-aided drug design.
www.openbiosim.org

We look forward to seeing you there!!
Sarah Harris, Sarah Fegan and Nicolas Foloppe



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[ccp4bb] CCPBioSim Industry Talk

[Sarah Fegan - STFC UKRI]

Hi all,

Registration is now open for our next Industry Talk. It will take place on 
Thursday 20 October 2022 from 2pm UK time. It will be on Zoom and registration 
is free but required to get the webinar link. The speakers are Alex R. Jones 
and Amy E. Danson from the National Physical Laboratory and the title is 
"Biomolecular Metrology: Ensuring Reproducible Measurement for the Life 
Sciences".

Details and registration can be found at https://www.ccpbiosim.ac.uk/npl2022.

Best wishes,
Sarah



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[ccp4bb] CCPBioSim Industry Talk

[Sarah Fegan - STFC UKRI]

Dear all,

Our next industry talk is on Wednesday 28 September 2022 at 2pm UK time. The 
speaker is John Liebeschuetz from Astex and his talk is "Do proteins ever 
strain drug-like ligands?"

Details and registration at https://www.ccpbiosim.ac.uk/astex2022. If you had 
registered for the talk in June that was cancelled because of illness and are 
still available and interested in attending, please register again.

Best wishes,
Sarah F



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Re: [ccp4bb] CCPBioSim Industry Talk

[Nigel Moriarty]

Thanks all for the notification it's not on. I guess I'll start my day an
hour earlier or just watch the sunrise.

Cheers

Nigel

---
Nigel W. Moriarty
Building 33R0349, Molecular Biophysics and Integrated Bioimaging
Lawrence Berkeley National Laboratory
Berkeley, CA 94720-8235
Phone : 510-486-5709 Email : nwmoria...@lbl.gov
Fax   : 510-486-5909  Web  : CCI.LBL.gov
ORCID : orcid.org/-0001-8857-9464


On Thu, Jun 30, 2022 at 6:10 AM Nigel Moriarty  wrote:

> Is this meeting still proceeding? My link doesn't work.
>
> Cheers
>
> Nigel
>
> ---
> Nigel W. Moriarty
> Building 33R0349, Molecular Biophysics and Integrated Bioimaging
> Lawrence Berkeley National Laboratory
> Berkeley, CA 94720-8235
> Phone : 510-486-5709 Email : nwmoria...@lbl.gov
> Fax   : 510-486-5909  Web  : CCI.LBL.gov
> ORCID : orcid.org/-0001-8857-9464
>
>
> On Fri, Jun 10, 2022 at 2:29 AM Sarah Fegan - STFC UKRI <
> 711df86179e2-dmarc-requ...@jiscmail.ac.uk> wrote:
>
>> Dear all,
>>
>> Our next online Industry Talk will be on Thursday 30 June 2022 at 2pm UK
>> time. The speaker is John Liebeschuetz from Astex and the title is "Do
>> proteins ever strain drug-like ligands?".
>>
>> Details and the registration link can be found at
>> www.ccpbiosim.ac.uk/astex2022.
>>
>>
>> *Abstract:* It is usually accepted that minimising ligand strain is
>> useful if one wishes to design potent ligand-efficient drugs. Yet there is
>> not yet full consensus how much strain energy can be acceptably
>> accommodated in a drug-like ligand. This talk will look at single-point and
>> dynamics-based methods for calculating strain energies from protein-ligand
>> complexes and discuss the considerable difficulties inherent in generating
>> accurate values.  An alternative approach will be presented whereby we
>> compare torsional ligand geometries in highly resolved protein-ligand
>> complexes,  with similar substructures in the Cambridge Structural Database
>> (1). This study led to the conclusion that we may need to reassess the
>> commonly held idea of a single principle binding pose.
>>
>>1. The Good, the Bad and the Twisted Revisited: An Analysis of ligand
>>geometry in Highly Resolved protein-Ligand X-Ray Structures. J.
>>W.Liebeschuetz, *J. Med. Chem*. 2021, *64*, 11, 7533-7543
>>
>> Best wishes,
>> Sarah
>>
>>
>>
>> --
>>
>> To unsubscribe from the CCP4BB list, click the following link:
>> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1
>>
>



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Re: [ccp4bb] CCPBioSim Industry Talk

[Nigel Moriarty]

Is this meeting still proceeding? My link doesn't work.

Cheers

Nigel

---
Nigel W. Moriarty
Building 33R0349, Molecular Biophysics and Integrated Bioimaging
Lawrence Berkeley National Laboratory
Berkeley, CA 94720-8235
Phone : 510-486-5709 Email : nwmoria...@lbl.gov
Fax   : 510-486-5909  Web  : CCI.LBL.gov
ORCID : orcid.org/-0001-8857-9464


On Fri, Jun 10, 2022 at 2:29 AM Sarah Fegan - STFC UKRI <
711df86179e2-dmarc-requ...@jiscmail.ac.uk> wrote:

> Dear all,
>
> Our next online Industry Talk will be on Thursday 30 June 2022 at 2pm UK
> time. The speaker is John Liebeschuetz from Astex and the title is "Do
> proteins ever strain drug-like ligands?".
>
> Details and the registration link can be found at
> www.ccpbiosim.ac.uk/astex2022.
>
>
> *Abstract:* It is usually accepted that minimising ligand strain is
> useful if one wishes to design potent ligand-efficient drugs. Yet there is
> not yet full consensus how much strain energy can be acceptably
> accommodated in a drug-like ligand. This talk will look at single-point and
> dynamics-based methods for calculating strain energies from protein-ligand
> complexes and discuss the considerable difficulties inherent in generating
> accurate values.  An alternative approach will be presented whereby we
> compare torsional ligand geometries in highly resolved protein-ligand
> complexes,  with similar substructures in the Cambridge Structural Database
> (1). This study led to the conclusion that we may need to reassess the
> commonly held idea of a single principle binding pose.
>
>1. The Good, the Bad and the Twisted Revisited: An Analysis of ligand
>geometry in Highly Resolved protein-Ligand X-Ray Structures. J.
>W.Liebeschuetz, *J. Med. Chem*. 2021, *64*, 11, 7533-7543
>
> Best wishes,
> Sarah
>
>
>
> --
>
> To unsubscribe from the CCP4BB list, click the following link:
> https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1
>



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[ccp4bb] CCPBioSim Industry Talk

[Sarah Fegan - STFC UKRI]

Dear all,

Registration is open for our Industry Talk titled "Championing the adoption of 
predictive sciences into the pharmaceutical discovery, process, and development 
space" by Ed Sherer from Merck. The talk will take place on Zoom (you will get 
the link after you register) Thursday 7 July 2022 at 2pm UK time.

Details and registration at 
www.ccpbiosim.ac.uk/merck2022

Abstract:  The role of computational chemistry for supporting the early drug 
discovery pipeline is well understood, and predictive sciences groups 
supporting medicinal chemistry from target identification to nomination of 
clinical candidates are commonplace in the pharmaceutical industry. Until 
recently, the role of computational prediction in the process, analytical, and 
development space was far less common. An overview will be presented covering 
how a team of computational chemists was established to prospectively impact 
areas such as organic reaction design, biocatalyst design, machine learning 
based catalyst design, stereochemical assignment, NMR characterization, green 
chemistry, determination of peptide macrocycle conformer ensembles, and small 
molecule crystal structure prediction. With a strong partnership between 
process chemists and computational chemists, we can drive excellence in organic 
chemistry for the pharmaceutical industry.

Best wishes,
Sarah



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[ccp4bb] CCPBioSim Industry Talk

[Sarah Fegan - STFC UKRI]

Dear all,

Our next online Industry Talk will be on Thursday 30 June 2022 at 2pm UK time. 
The speaker is John Liebeschuetz from Astex and the title is "Do proteins ever 
strain drug-like ligands?".

Details and the registration link can be found at 
www.ccpbiosim.ac.uk/astex2022.


Abstract: It is usually accepted that minimising ligand strain is useful if one 
wishes to design potent ligand-efficient drugs. Yet there is not yet full 
consensus how much strain energy can be acceptably accommodated in a drug-like 
ligand. This talk will look at single-point and dynamics-based methods for 
calculating strain energies from protein-ligand complexes and discuss the 
considerable difficulties inherent in generating accurate values.  An 
alternative approach will be presented whereby we compare torsional ligand 
geometries in highly resolved protein-ligand complexes,  with similar 
substructures in the Cambridge Structural Database (1). This study led to the 
conclusion that we may need to reassess the commonly held idea of a single 
principle binding pose.

  1.  The Good, the Bad and the Twisted Revisited: An Analysis of ligand 
geometry in Highly Resolved protein-Ligand X-Ray Structures. J. W.Liebeschuetz, 
J. Med. Chem. 2021, 64, 11, 7533-7543

Best wishes,
Sarah





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https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1

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[ccp4bb] CCPBioSim Industry Talk

[Sarah Fegan - STFC UKRI]

Dear Colleagues,

The next event in the Industry Talk Series will take place online 13 April 2022 
at 3pm (British Summer Time). The title is "Adopting a collaborative mindset in 
industrial drug discovery in the AI era" and the speakers are Ewa Chudyk and 
Meir Glick from Vertex Pharmaceuticals, see abstract below.

The registration deadline is 11 April 2022. The registration link and all 
details can be found at https://www.ccpbiosim.ac.uk/collaboration22.

Best wishes,
Sarah


Abstract:

The discovery of a new drug is a complex and expensive process, involving the 
collaboration of many interdisciplinary teams of scientists. Along the way, 
computational chemists can contribute to and accelerate the decision-making 
process by assessing available data with relevant analysis methods. At various 
stages of the process, this usually involves partnering with medicinal 
chemists, DMPK scientists, biologists, toxicologists, and formulation 
scientists, amongst others. Applying “predict first” solutions involves 
reaching for both traditional computational chemistry tools as well as novel 
AI-based methods when working as part of these interdisciplinary teams to 
identify opportunities of the highest potential impact on the project. 
Appropriate models are then applied for given hypotheses and assessed after 
experiments are performed.

In this talk, we will give a general overview of the Vertex Pharmaceuticals 
drug discovery approach. We will also provide a computational chemist’s 
perspective based on our own experience in the industry. This will include 
diverse examples of computational methods used depending on the project’s 
needs. These consist of mining large datasets, building machine learning-based 
predictive models, docking virtual compound databases, including quantum 
chemistry calculations in chemical synthesis planning, running molecular 
simulations of large protein complexes, or using deep learning models for cell 
segmentation image recognition, amongst others. We will also share practical 
considerations of working in the industry, such as project timescales or 
partnering with interdisciplinary experimental teams. Finally, we will discuss 
the impact of collaboration, both within the industry and with academia to seek 
innovative solutions to complex problems.


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[ccp4bb] CCPBioSim Industry Talk: Final reminder

[Sarah Fegan - STFC UKRI]

Hi everyone,

I would like to remind you that the registration deadline for the next industry 
talk is 24 November (Wednesday). The talk is "Scientific hypothesis-building 
through visualisation using the example of a newly observed phenomenon in 
COVID-19 patients" by Anncharlott V. BERGLAR from the Scientific Visualisation 
Lab.

Details and registration can be found here: 
https://www.ccpbiosim.ac.uk/scivislab21

Please feel free to share this with anyone who might be interested.

Friday 26 November 2021, 14:00 - 15:30 GMT
Abstract:
Traditionally, scientific visualisation is a method of recording scientific 
data and contents. One step further, visualisation and design techniques can 
complement the scientific method by providing new perspectives and by 
supporting the generation of new ideas. Holding a PhD in biomolecular sciences 
and a MA in scientific illustration, Anncharlott is a freelance scientific 
illustrator and with her knowledge in both fields she aims at contributing to 
the gain of scientific insight in the molecular world.
The Bloch lab recently observed moderate to heavy deformations of red blood 
cells (RBCs) in COVID-19 patients, which we think contribute to the clotting 
events that commonly occur over the course of the disease. The cause or 
mechanism of this observation at a molecular level, however, is unknown. We 
combine classical and state-of-the-art visualisation techniques for 
hypothesis-building, experimental design, and to gain insight into the 
molecular scenery around the RBC membrane when in contact with a SARS-CoV-2 
virus.
Methods such as 3D visualisation, 3D printing and sketching, in combination 
with protein docking and other in-silico experiments allowed building a working 
hypothesis of the mechanism of action underlying the observed RBC deformations. 
Additionally, our approach resulted in communicable and appealing visuals that 
can be used for various purposes and that are able to feature and promote our 
research to the desired target audience.

Best wishes,
Sarah

This email and any attachments are intended solely for the use of the named 
recipients. If you are not the intended recipient you must not use, disclose, 
copy or distribute this email or any of its attachments and should notify the 
sender immediately and delete this email from your system. UK Research and 
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this email or any attachments containing viruses or malware but the recipient 
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the recipient may sustain due to presence of any viruses.




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[ccp4bb] CCPBioSim Industry Talk

[Sarah Fegan - STFC UKRI]

Dear all,

Registration is now open for our next industry talk, details and the 
registration link can be found at 
www.ccpbiosim.ac.uk/scivislab21. The 
talk will take place at 2pm GMT on Friday 26 November 2021 (registration 
deadline 24 November). Anncharlott Berglar from the Scientific Visualisation 
Lab will talk about "Scientific hypothesis-building through visualisation using 
the example of a newly observed phenomenon in COVID-19 patients".

Abstract: Traditionally, scientific visualisation is a method of recording 
scientific data and contents. One step further, visualisation and design 
techniques can complement the scientific method by providing new perspectives 
and by supporting the generation of new ideas. Holding a PhD in biomolecular 
sciences and a MA in scientific illustration, Anncharlott is a freelance 
scientific illustrator and with her knowledge in both fields she aims at 
contributing to the gain of scientific insight in the molecular world.

The Bloch lab recently observed moderate to heavy deformations of red blood 
cells (RBCs) in COVID-19 patients, which we think contribute to the clotting 
events that commonly occur over the course of the disease. The cause or 
mechanism of this observation at a molecular level, however, is unknown. We 
combine classical and state-of-the-art visualisation techniques for 
hypothesis-building, experimental design, and to gain insight into the 
molecular scenery around the RBC membrane when in contact with a SARS-CoV-2 
virus.

Methods such as 3D visualisation, 3D printing and sketching, in combination 
with protein docking and other in-silico experiments allowed building a working 
hypothesis of the mechanism of action underlying the observed RBC deformations. 
Additionally, our approach resulted in communicable and appealing visuals that 
can be used for various purposes and that are able to feature and promote our 
research to the desired target audience.

Best wishes,
Sarah



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recipients. If you are not the intended recipient you must not use, disclose, 
copy or distribute this email or any of its attachments and should notify the 
sender immediately and delete this email from your system. UK Research and 
Innovation (UKRI) has taken every reasonable precaution to minimise risk of 
this email or any attachments containing viruses or malware but the recipient 
should carry out its own virus and malware checks before opening the 
attachments. UKRI does not accept any liability for any losses or damages which 
the recipient may sustain due to presence of any viruses.




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[ccp4bb] CCPBioSim Industry Talk

[Sarah Fegan - STFC UKRI]

Dear all,

We are pleased to announce that our next industrial speaker will be Nicolas 
Foloppe from Vernalis. The talk will be on 26 August 2021 at 2pm British time 
(registration is free but required by 24 August 2021). Details and registration 
can be found at https://www.ccpbiosim.ac.uk/binding2021.


Title: Characterising the unbound state of drug-like compounds: implications 
for molecular recognition

Abstract: The unbound state of drug compounds is important to better understand 
their binding to proteins, including conformational preorganization and the 
intramolecular reorganization energy of compounds upon binding (ΔEReorg). These 
questions were addressed with molecular dynamics (MD) simulations of diverse 
compounds, unbound or complexed to their protein target. Analysis of those 
systems involved observations regarding their electrostatics.

The unbound compounds simulated with MD were compared to conformers 
generated with implicit generalized Born (GB) aqueous solvation models. The 
notion of conformational pre-organization for binding was investigated by 
comparing the simulated compounds to their bioactive X-ray structure. The study 
yielded low to moderate values of ΔEReorg for most, but not all, compounds. For 
three particularly polar compounds, ΔEReorg was substantial (≥ 15 kcal/mol). 
Those large ΔEReorg values may be interpreted as a redistribution of 
electrostatic interactions upon binding.


Best wishes,
Sarah

This email and any attachments are intended solely for the use of the named 
recipients. If you are not the intended recipient you must not use, disclose, 
copy or distribute this email or any of its attachments and should notify the 
sender immediately and delete this email from your system. UK Research and 
Innovation (UKRI) has taken every reasonable precaution to minimise risk of 
this email or any attachments containing viruses or malware but the recipient 
should carry out its own virus and malware checks before opening the 
attachments. UKRI does not accept any liability for any losses or damages which 
the recipient may sustain due to presence of any viruses.




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