Alberto Cuzzolin
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View article: Unbinding Kinetics of Muscarinic M3 Receptor Antagonists Explained by Metadynamics Simulations
Unbinding Kinetics of Muscarinic M3 Receptor Antagonists Explained by Metadynamics Simulations Open
The residence time (RT), the time for which a drug remains bound to its biological target, is a critical parameter for drug design. The prediction of this key kinetic property has been proven to be challenging and computationally demanding…
View article: Computationally driven discovery of SARS-CoV-2 M<sup>pro</sup>inhibitors: from design to experimental validation
Computationally driven discovery of SARS-CoV-2 M<sup>pro</sup>inhibitors: from design to experimental validation Open
The dominant binding mode of the QUB-00006-Int-07 main protease inhibitor during absolute binding free energy simulations.
View article: Computationally driven discovery of SARS-CoV-2 Mpro inhibitors: from design to experimental validation (preprint)
Computationally driven discovery of SARS-CoV-2 Mpro inhibitors: from design to experimental validation (preprint) Open
We report the fast-track computationally-driven discovery of new SARS-CoV2 Main Protease (Mpro) inhibitors whose potency range from mM for initial non-covalent ligands to high nM for the final covalent compound (IC50=830 +/-50 nM). The pro…
View article: A Deep-Learning Approach toward Rational Molecular Docking Protocol Selection
A Deep-Learning Approach toward Rational Molecular Docking Protocol Selection Open
While a plethora of different protein–ligand docking protocols have been developed over the past twenty years, their performances greatly depend on the provided input protein–ligand pair. In this study, we developed a machine-learning mode…
View article: SkeleDock: A Web Application for Scaffold Docking in PlayMolecule
SkeleDock: A Web Application for Scaffold Docking in PlayMolecule Open
SkeleDock is a scaffold docking algorithm which uses the structure of a protein-ligand complex as a template to model the binding mode of a chemically similar system. This algorithm was evaluated in the D3R Grand Challenge 4 pose predictio…
View article: SkeleDock: A Web Application for Scaffold Docking\nin PlayMolecule
SkeleDock: A Web Application for Scaffold Docking\nin PlayMolecule Open
SkeleDock is a scaffold docking algorithm\nwhich uses the structure\nof a protein–ligand complex as a template to model the binding\nmode of a chemically similar system. This algorithm was evaluated\nin the D3R Grand Challenge 4 pose predi…
View article: A Deep-Learning Approach Toward Rational Molecular Docking Protocol Selection
A Deep-Learning Approach Toward Rational Molecular Docking Protocol Selection Open
While a plethora of different protein-ligand docking protocols have been developed over the past twenty years, their performances greatly depend on the provided input protein-ligand pair. In this work we have developed a machine-learning m…
View article: A Deep-Learning Approach Toward Rational Molecular Docking Protocol Selection
A Deep-Learning Approach Toward Rational Molecular Docking Protocol Selection Open
While a plethora of different protein-ligand docking protocols have been developed over the past twenty years, their performances greatly depend on the provided input protein-ligand pair. In this work we have developed a machine-learning m…
View article: Reconstruction of apo A2A receptor activation pathways reveal ligand-competent intermediates and state-dependent cholesterol hotspots
Reconstruction of apo A2A receptor activation pathways reveal ligand-competent intermediates and state-dependent cholesterol hotspots Open
View article: Can We Still Trust Docking Results? An Extension of the Applicability of DockBench on PDBbind Database
Can We Still Trust Docking Results? An Extension of the Applicability of DockBench on PDBbind Database Open
The number of entries in the Protein Data Bank (PDB) has doubled in the last decade, and it has increased tenfold in the last twenty years. The availability of an ever-growing number of structures is having a huge impact on the Structure-B…
View article: Cover Feature: AquaMMapS: An Alternative Tool to Monitor the Role of Water Molecules During Protein–Ligand Association (ChemMedChem 6/2018)
Cover Feature: AquaMMapS: An Alternative Tool to Monitor the Role of Water Molecules During Protein–Ligand Association (ChemMedChem 6/2018) Open
The Cover Feature shows the different behavior of structural water molecules and bulk water. We have developed the AquaMMapS tool, which is able to identify stationary hydration sites close to the protein surface starting from molecular dy…
View article: Optimizing Proteins and Ligands for Computerized Drug Discovery
Optimizing Proteins and Ligands for Computerized Drug Discovery Open
The reliability of physics-based in-silico studies of protein-ligand complexes highly depends on the quality of available structures and force-field parameters. Both these subjects have been largely addressed by both experimental and compu…
View article: Synthesis and preliminary structure-activity relationship study of 2-aryl-2<i>H</i>-pyrazolo[4,3-<i>c</i>]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
Synthesis and preliminary structure-activity relationship study of 2-aryl-2<i>H</i>-pyrazolo[4,3-<i>c</i>]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors Open
The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour effica…
View article: AquaMMapS: An Alternative Tool to Monitor the Role of Water Molecules During Protein–Ligand Association
AquaMMapS: An Alternative Tool to Monitor the Role of Water Molecules During Protein–Ligand Association Open
Unquestionably, water appears to be an active player in the noncovalent protein–ligand binding process, as it can either bridge interactions between protein and ligand or can be replaced by the bound ligand. Accordingly, in the last decade…
View article: Synthesis and preliminary structure-activity relationship study of 2-aryl-2<i>H</i>-pyrazolo[4,3-<i>c</i>]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors
Synthesis and preliminary structure-activity relationship study of 2-aryl-2<i>H</i>-pyrazolo[4,3-<i>c</i>]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors Open
The serine-threonine checkpoint kinase 1 (Chk1) plays a critical role in the cell cycle arrest in response to DNA damage. In the last decade, Chk1 inhibitors have emerged as a novel therapeutic strategy to potentiate the anti-tumour effica…
View article: Novel in silico approaches to depict the protein-ligand recognition events
Novel in silico approaches to depict the protein-ligand recognition events Open
The discovery and commercialization of a new drug is a long and expensive process. Such process is divided into different phases during which the phisico-chemical and therapeutic properties of the compounds are determined. In particular, t…
View article: INDEL mutants increase NPM-ALK sensitivity to crizotinib.
INDEL mutants increase NPM-ALK sensitivity to crizotinib. Open
HEK-293T cells were transfected with WT NPM-ALK alone or in combination with D309H-OOF, Δ276–299, S232R-OOF and R308-Ins8 mutants. (A) Total and phosphorylated NPM-ALK levels are shown before and after exposure to crizotinib (0.5, 1…
View article: DockBench: An Integrated Informatic Platform Bridging the Gap between the Robust Validation of Docking Protocols and Virtual Screening Simulations
DockBench: An Integrated Informatic Platform Bridging the Gap between the Robust Validation of Docking Protocols and Virtual Screening Simulations Open
Virtual screening (VS) is a computational methodology that streamlines the drug discovery process by reducing costs and required resources through the in silico identification of potential drug candidates. Structure-based VS (SBVS) exploit…
View article: ALK Kinase Domain Mutations in Primary Anaplastic Large Cell Lymphoma: Consequences on NPM-ALK Activity and Sensitivity to Tyrosine Kinase Inhibitors
ALK Kinase Domain Mutations in Primary Anaplastic Large Cell Lymphoma: Consequences on NPM-ALK Activity and Sensitivity to Tyrosine Kinase Inhibitors Open
ALK inhibitor crizotinib has shown potent antitumor activity in children with refractory Anaplastic Large Cell Lymphoma (ALCL) and the opportunity to include ALK inhibitors in first-line therapies is oncoming. However, recent studies sugge…