Recent PELE Developments and Applications in Drug Discovery Campaigns
Abstract
:1. Introduction
2. Molecular Modelling Advances
3. Combining ML and MM
3.1. MM Data Augmentation Enhances ML Downstream Tasks
3.2. Directed Generation of New Chemical Entities
3.3. Screening of Ultra-Large Databases
4. Combining fragPELE and aquaPELE
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
CADD | Computer-Aided Drug Design |
RNA | Ribonucleic Acid |
DNA | Deoxyribunocleic Acid |
ADMET | Chemical absorption, distribution, metabolism, excretion, and toxicity |
MM | Molecular Modelling |
ML | Machine Learning |
MC | Monte Carlo |
FEP | Free Energy Perturbation |
PELE | Protein Energy Landscape Exploration |
CSAR | Community Structure-Activity Resource |
BSC | Barcelona Supercomputing Center |
MD | Molecular Dynamics |
MDFP | Molecular Dynamic Finger Prints |
QED | Quantitative Estimate of Druglikeness |
SA | Synthesis Accessibility |
B | Billion |
HPC | High Performance Computing |
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Systems | Scaffold | Growing | |||||
---|---|---|---|---|---|---|---|
PDB Scaffold | Water ID | PDB Grown | |||||
HSP90 (1) | 3RLQ | A249 | 1.0 | 1.84 | 3RLR | −0.45 | |
A286 | 1.25 | - | |||||
HSP90 (2) | 2XAB | A2246 | 1.0 | ✓ | 2XJG | −1.0 | |
A2115 | 0.60 | ✓ | +0.05 | ||||
BRD4 | 5I80 | A319 | 0.85 | ✓ | 5I88 | −0.85 | |
A336 | 0.29 | ✓ | −0.29 | ||||
TAF1 | 5I29 | A1891 | 0.16 | ✓ | 5I1Q | A1891: −0.13 | |
A1860: −0.79 | |||||||
A1860 | 0.84 | ✓ | 6BQD | A1891: −0.16 | |||
A1860: −0.71 | |||||||
SiaP WT | 2V4C | A2346 | 0.07 | ✓ | 3B50 | −0.07 | |
CHK1 | 2C3L | A2056 | 0.02 | ✓ | 2C3K | −0.02 | |
A2127 | 1.0 | 1.44 | −0.91 | ||||
A2052 | 0.07 | 1.52 | −0.07 | ||||
A2043 | 0.02 | 1.98 | −0.02 | ||||
Control | HSP90 (1) | 3RLQ | A249 | 1.0 | 1.84 | - | +0.03 |
A286 | 1.25 | 0.0 | |||||
HSP90 (2) | - | A1 | 1.0 | ✓ | 3RLP | −0.03 | |
A3 | 0.8 | ✓ | +0.20 |
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Puch-Giner, I.; Molina, A.; Municoy, M.; Pérez, C.; Guallar, V. Recent PELE Developments and Applications in Drug Discovery Campaigns. Int. J. Mol. Sci. 2022, 23, 16090. https://doi.org/10.3390/ijms232416090
Puch-Giner I, Molina A, Municoy M, Pérez C, Guallar V. Recent PELE Developments and Applications in Drug Discovery Campaigns. International Journal of Molecular Sciences. 2022; 23(24):16090. https://doi.org/10.3390/ijms232416090
Chicago/Turabian StylePuch-Giner, Ignasi, Alexis Molina, Martí Municoy, Carles Pérez, and Victor Guallar. 2022. "Recent PELE Developments and Applications in Drug Discovery Campaigns" International Journal of Molecular Sciences 23, no. 24: 16090. https://doi.org/10.3390/ijms232416090