Computer-aided drug discovery

1992 ◽  
Vol 99 (1-2) ◽  
pp. 105-111 ◽  
Author(s):  
W. Graham Richards
Keyword(s):  
Free Energy ◽  
Protein Structure ◽  
Drug Discovery ◽  
Molecular Similarity ◽  
Binding Free Energy ◽  
Protein Crystal ◽  
Crystal Data ◽  
Target Structure ◽  
Computer Aided

Synopsis:The role of computers in drug discovery depends on just how much is known about the target macromolecule. If atomic detail of the receptor is known, binding free energy differences between drug variants may be computed. Major effort is being expended in extending the area of applicability of such studies by predicting protein structure based on homologies with known protein crystal data. Where no target structure is available, computational methods can provide leads by defining transition state structures and then using the approach of molecular similarity to define stable mimics to act as blockers.

Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects

2020 ◽  
Author(s):  
Christina Schindler ◽  
Hannah Baumann ◽  
Andreas Blum ◽  
Dietrich Böse ◽  
Hans-Peter Buchstaller ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Large Scale ◽  
Active Drug ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Energy Calculation ◽  
Large Scale Assessment ◽  
New Public ◽  
Binding Free Energy Calculations

Here we present an evaluation of the binding affinity prediction accuracy of the free energy calculation method FEP+ on internal active drug discovery projects and on a large new public benchmark set.<br>

scholarly journals Binding free energy predictions in host-guest systems using Autodock4. A retrospective analysis on SAMPL6, SAMPL7 and SAMPL8 challenges

2021 ◽  
Author(s):  
Lorenzo Casbarra ◽  
Piero Procacci
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Drug Discovery ◽  
Binding Free Energy ◽  
Cost Ratio ◽  
Benefit Cost Ratio ◽  
Docking Program ◽  
Benefit Cost ◽  
Overall Reliability ◽  
Absolute Binding Free Energy

AbstractWe systematically tested the Autodock4 docking program for absolute binding free energy predictions using the host-guest systems from the recent SAMPL6, SAMPL7 and SAMPL8 challenges. We found that Autodock4 behaves surprisingly well, outperforming in many instances expensive molecular dynamics or quantum chemistry techniques, with an extremely favorable benefit-cost ratio. Some interesting features of Autodock4 predictions are revealed, yielding valuable hints on the overall reliability of docking screening campaigns in drug discovery projects.

scholarly journals Alchemical Absolute Protein-Ligand Binding Free Energies for Drug Design

2021 ◽  
Author(s):  
Yuriy Khalak ◽  
Gary Tresdern ◽  
Matteo Aldeghi ◽  
Hannah Magdalena Baumann ◽  
David L. Mobley ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Drug Design ◽  
Ligand Binding ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Free Energies ◽  
Energy Calculations ◽  
Binding Free Energy Calculations ◽  
Binding Free Energies

The recent advances in relative protein-ligand binding free energy calculations have shown the value of alchemical methods in drug discovery. Accurately assessing absolute binding free energies, although highly desired, remains...

scholarly journals On the Role of Dewetting Transitions in Host–Guest Binding Free Energy Calculations

2012 ◽  
Vol 9 (1) ◽  
pp. 46-53 ◽  
Author(s):  
Kathleen E. Rogers ◽  
Juan Manuel Ortiz-Sánchez ◽  
Riccardo Baron ◽  
Mikolai Fajer ◽  
César Augusto F. de Oliveira ◽  
...  
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Energy Calculations ◽  
Guest Binding ◽  
Binding Free Energy Calculations

Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects

2020 ◽  
Author(s):  
Christina Schindler ◽  
Hannah Baumann ◽  
Andreas Blum ◽  
Dietrich Böse ◽  
Hans-Peter Buchstaller ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Large Scale ◽  
Active Drug ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Energy Calculation ◽  
Large Scale Assessment ◽  
New Public ◽  
Binding Free Energy Calculations

Here we present an evaluation of the binding affinity prediction accuracy of the free energy calculation method FEP+ on internal active drug discovery projects and on a large new public benchmark set.<br>

Large-Scale Assessment of Binding Free Energy Calculations in Active Drug Discovery Projects

2020 ◽  
Vol 60 (11) ◽  
pp. 5457-5474 ◽  
Author(s):  
Christina E. M. Schindler ◽  
Hannah Baumann ◽  
Andreas Blum ◽  
Dietrich Böse ◽  
Hans-Peter Buchstaller ◽  
...  
Keyword(s):  
Free Energy ◽  
Drug Discovery ◽  
Large Scale ◽  
Active Drug ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Energy Calculations ◽  
Large Scale Assessment ◽  
Scale Assessment ◽  
Binding Free Energy Calculations

scholarly journals Fitting quantum machine learning potentials to experimental free energy data: Predicting tautomer ratios in solution

2021 ◽  
Author(s):  
Marcus Wieder ◽  
Josh Fass ◽  
John D. Chodera
Keyword(s):  
Machine Learning ◽  
Free Energy ◽  
Drug Discovery ◽  
Energy Data ◽  
Quantum Machine Learning ◽  
Computer Aided ◽  
Approved Drugs

The computation of tautomer ratios of druglike molecules is enormously important in computer-aided drug discovery, as over a quarter of all approved drugs can populate multiple tautomeric species in solution....

scholarly journals A Cloud Computing Platform for Scalable Relative and Absolute Binding Free Energy Prediction: New Opportunities and Challenges for Drug Discovery

2020 ◽  
Author(s):  
Zhixiong Lin ◽  
Junjie Zou ◽  
Chunwang Peng ◽  
Shuai Liu ◽  
Zhipeng Li ◽  
...  
Keyword(s):  
Cloud Computing ◽  
Free Energy ◽  
Drug Discovery ◽  
Large Scale ◽  
Binding Free Energy ◽  
Energy Prediction ◽  
Biological Targets ◽  
Computing Platform ◽  
Cloud Computing Platform ◽  
Hit Identification

<p>Free energy perturbation (FEP) has become widely used in drug discovery programs for binding affinity prediction between candidate compounds and their biological targets. Simultaneously limitations of FEP applications also exist, including but not limited to, the high cost, long waiting time, limited scalability and application scenarios. To overcome these problems, we have developed a scalable cloud computing platform (XFEP) for both relative and absolute free energy predictions with refined simulation protocols. XFEP enables large-scale FEP calculations in a more efficient, scalable and affordable way, e.g. the evaluation of 5,000 compounds can be performed in one week using 50-100 GPUs with a computing cost approximately corresponding to the cost for one new compound synthesis. Together with artificial intelligence (AI) techniques for goal-directed molecule generation and evaluation, new opportunities can be explored for FEP applications in the drug discovery stages of hit identification, hit-to-lead, and lead optimization with R-group substitutions, scaffold hopping, and completely different molecule evaluation. We anticipate scalable FEP applications will become widely used in more drug discovery projects to speed up the drug discovery process from hit identification to pre-clinical candidate compound nomination. </p>

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