{"entity": "researcher", "timestamp": "2026-08-20T21:05:02.092Z", "family": "Carloni", "given": "Paolo", "initials": "P", "orcid": "0000-0002-9010-0149", "affiliations": ["Institute for Neuroscience and Medicine (INM\u20109) and Institute for Advanced Simulations (IAS\u20105) \u201cComputational biomedicine\u201d Forschungszentrum J\u00fclich  J\u00fclich Germany", "INM\u201011 JARA\u2010Institute: Molecular Neuroscience and Neuroimaging Forschungszentrum J\u00fclich  J\u00fclich Germany"], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/b0d0a3cc3e0a4f38b52e681b8ee0c6c7.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/b0d0a3cc3e0a4f38b52e681b8ee0c6c7"}}, "publications": [{"entity": "publication", "iuid": "336dfbab8d9f4359a6df4d224f9deafa", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/336dfbab8d9f4359a6df4d224f9deafa.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/336dfbab8d9f4359a6df4d224f9deafa"}}, "title": "Multiscale molecular simulations to investigate adenylyl cyclase\u2010based signaling in the brain", "authors": [{"family": "van Keulen", "given": "Siri C", "initials": "SC", "orcid": "0000-0001-6995-8389", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/838c25a32bf64d748878f2e1cd8f6227.json"}}, {"family": "Martin", "given": "Juliette", "initials": "J", "orcid": "0000-0002-4787-0885", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/275f6d37420a4a9686333e3cf5ee0486.json"}}, {"family": "Colizzi", "given": "Francesco", "initials": "F", "orcid": "0000-0001-5601-1452", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b77167bd9a574db4aaf988820337fffc.json"}}, {"family": "Frezza", "given": "Elisa", "initials": "E", "orcid": "0000-0003-0122-7859", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1b13ebd77c5e45cf8b5cdd7d20537e4e.json"}}, {"family": "Trpevski", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9068-6744", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b007cf92b2cb4bc8a4c61436e4e3cefc.json"}}, {"family": "Diaz", "given": "Nuria Cirauqui", "initials": "NC", "orcid": "0000-0003-4752-9916", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/23e47b48ccf2426c8d2eb0a43115b7cb.json"}}, {"family": "Vidossich", "given": "Pietro", "initials": "P"}, {"family": "Rothlisberger", "given": "Ursula", "initials": "U", "orcid": "0000-0002-1704-8591", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/05288e7d55aa42508609d4e97065edeb.json"}}, {"family": "Hellgren Kotaleski", "given": "Jeanette", "initials": "J", "orcid": "0000-0002-0550-0739", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a920517bd1c142878f03bee05e843b62.json"}}, {"family": "Wade", "given": "Rebecca C", "initials": "RC", "orcid": "0000-0001-5951-8670", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/502d793871ee450e9b3961a027d3199d.json"}}, {"family": "Carloni", "given": "Paolo", "initials": "P", "orcid": "0000-0002-9010-0149", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b0d0a3cc3e0a4f38b52e681b8ee0c6c7.json"}}], "type": "journal-article", "published": "2023-01-00", "journal": {"title": "Wiley Interdiscip Rev Comput Mol Sci", "issn": "1759-0876", "volume": "13", "issue": "1", "issn-l": null}, "abstract": null, "doi": "10.1002/wcms.1623", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T06:35:59.164Z", "modified": "2026-08-20T06:35:59.536Z"}, {"entity": "publication", "iuid": "cedb0bb29a7443ffa037f3dc237a6526", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cedb0bb29a7443ffa037f3dc237a6526.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cedb0bb29a7443ffa037f3dc237a6526"}}, "title": "A Blueprint for High Affinity SARS-CoV-2 Mpro Inhibitors from Activity-Based Compound Library Screening Guided by Analysis of Protein Dynamics.", "authors": [{"family": "Gossen", "given": "Jonas", "initials": "J", "orcid": "0000-0002-0730-6796", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/19eb289f11c5427e914bd13bdf8ae3dd.json"}}, {"family": "Albani", "given": "Simone", "initials": "S"}, {"family": "Hanke", "given": "Anton", "initials": "A"}, {"family": "Joseph", "given": "Benjamin P", "initials": "BP"}, {"family": "Bergh", "given": "Cathrine", "initials": "C"}, {"family": "Kuzikov", "given": "Maria", "initials": "M", "orcid": "0000-0001-8771-1865", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f75fc6caafe4ebbb876387123b84608.json"}}, {"family": "Costanzi", "given": "Elisa", "initials": "E"}, {"family": "Manelfi", "given": "Candida", "initials": "C"}, {"family": "Storici", "given": "Paola", "initials": "P"}, {"family": "Gribbon", "given": "Philip", "initials": "P"}, {"family": "Beccari", "given": "Andrea R", "initials": "AR"}, {"family": "Talarico", "given": "Carmine", "initials": "C"}, {"family": "Spyrakis", "given": "Francesca", "initials": "F", "orcid": "0000-0002-4016-227X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ae9bda7fd7a44ca78986a5ebb98e4ec6.json"}}, {"family": "Lindahl", "given": "Erik", "initials": "E"}, {"family": "Zaliani", "given": "Andrea", "initials": "A", "orcid": "0000-0002-1740-8390", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/43d815becc3740cd813a0ec55374a385.json"}}, {"family": "Carloni", "given": "Paolo", "initials": "P", "orcid": "0000-0002-9010-0149", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b0d0a3cc3e0a4f38b52e681b8ee0c6c7.json"}}, {"family": "Wade", "given": "Rebecca C", "initials": "RC", "orcid": "0000-0001-5951-8670", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/502d793871ee450e9b3961a027d3199d.json"}}, {"family": "Musiani", "given": "Francesco", "initials": "F", "orcid": "0000-0003-0200-1712", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9bbe3ee421554bb685d04e91f20e5d51.json"}}, {"family": "Kokh", "given": "Daria B", "initials": "DB", "orcid": "0000-0002-4687-6572", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7b2a541d1ab84ad1814847821e177c6b.json"}}, {"family": "Rossetti", "given": "Giulia", "initials": "G", "orcid": "0000-0002-2032-4630", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7c4982dcb9494915a3cf34dbc2a0c310.json"}}], "type": "journal article", "published": "2021-06-11", "journal": {"title": "ACS pharmacology & translational science", "issn": "2575-9108", "volume": "4", "issue": "3", "pages": "1079-1095", "issn-l": "2575-9108"}, "abstract": "The SARS-CoV-2 coronavirus outbreak continues to spread at a rapid rate worldwide. The main protease (Mpro) is an attractive target for anti-COVID-19 agents. Unexpected difficulties have been encountered in the design of specific inhibitors. Here, by analyzing an ensemble of \u223c30 000 SARS-CoV-2 Mpro conformations from crystallographic studies and molecular simulations, we show that small structural variations in the binding site dramatically impact ligand binding properties. Hence, traditional druggability indices fail to adequately discriminate between highly and poorly druggable conformations of the binding site. By performing \u223c200 virtual screenings of compound libraries on selected protein structures, we redefine the protein's druggability as the consensus chemical space arising from the multiple conformations of the binding site formed upon ligand binding. This procedure revealed a unique SARS-CoV-2 Mpro blueprint that led to a definition of a specific structure-based pharmacophore. The latter explains the poor transferability of potent SARS-CoV Mpro inhibitors to SARS-CoV-2 Mpro, despite the identical sequences of the active sites. Importantly, application of the pharmacophore predicted novel high affinity inhibitors of SARS-CoV-2 Mpro, that were validated by in vitro assays performed here and by a newly solved X-ray crystal structure. These results provide a strong basis for effective rational drug design campaigns against SARS-CoV-2 Mpro and a new computational approach to screen protein targets with malleable binding sites.", "doi": "10.1021/acsptsci.0c00215", "pmid": "34136757", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8009102"}], "notes": [], "created": "2026-08-20T08:12:56.329Z", "modified": "2026-08-20T08:13:20.386Z"}, {"entity": "publication", "iuid": "bf713b4be054448b837f0f3744038238", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/bf713b4be054448b837f0f3744038238.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/bf713b4be054448b837f0f3744038238"}}, "title": "Regulation of adenylyl cyclase 5 in striatal neurons confers the ability to detect coincident neuromodulatory signals.", "authors": [{"family": "Bruce", "given": "Neil J", "initials": "NJ", "orcid": "0000-0002-2735-3215", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3533ee5106064d07a14f9bf6334de21e.json"}}, {"family": "Narzi", "given": "Daniele", "initials": "D"}, {"family": "Trpevski", "given": "Daniel", "initials": "D"}, {"family": "van Keulen", "given": "Siri C", "initials": "SC", "orcid": "0000-0001-6995-8389", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/838c25a32bf64d748878f2e1cd8f6227.json"}}, {"family": "Nair", "given": "Anu G", "initials": "AG", "orcid": "0000-0002-1952-9583", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5a923f8455b54b32b90949faa67ea90c.json"}}, {"family": "R\u00f6thlisberger", "given": "Ursula", "initials": "U"}, {"family": "Wade", "given": "Rebecca C", "initials": "RC", "orcid": "0000-0001-5951-8670", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/502d793871ee450e9b3961a027d3199d.json"}}, {"family": "Carloni", "given": "Paolo", "initials": "P", "orcid": "0000-0002-9010-0149", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b0d0a3cc3e0a4f38b52e681b8ee0c6c7.json"}}, {"family": "Hellgren Kotaleski", "given": "Jeanette", "initials": "J", "orcid": "0000-0002-0550-0739", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a920517bd1c142878f03bee05e843b62.json"}}], "type": "journal article", "published": "2019-10-00", "journal": {"title": "PLoS Comput Biol", "issn": "1553-7358", "volume": "15", "issue": "10", "pages": "e1007382", "issn-l": "1553-734X"}, "abstract": "Long-term potentiation and depression of synaptic activity in response to stimuli is a key factor in reinforcement learning. Strengthening of the corticostriatal synapses depends on the second messenger cAMP, whose synthesis is catalysed by the enzyme adenylyl cyclase 5 (AC5), which is itself regulated by the stimulatory G\u03b1olf and inhibitory G\u03b1i proteins. AC isoforms have been suggested to act as coincidence detectors, promoting cellular responses only when convergent regulatory signals occur close in time. However, the mechanism for this is currently unclear, and seems to lie in their diverse regulation patterns. Despite attempts to isolate the ternary complex, it is not known if G\u03b1olf and G\u03b1i can bind to AC5 simultaneously, nor what activity the complex would have. Using protein structure-based molecular dynamics simulations, we show that this complex is stable and inactive. These simulations, along with Brownian dynamics simulations to estimate protein association rates constants, constrain a kinetic model that shows that the presence of this ternary inactive complex is crucial for AC5's ability to detect coincident signals, producing a synergistic increase in cAMP. These results reveal some of the prerequisites for corticostriatal synaptic plasticity, and explain recent experimental data on cAMP concentrations following receptor activation. Moreover, they provide insights into the regulatory mechanisms that control signal processing by different AC isoforms.", "doi": "10.1371/journal.pcbi.1007382", "pmid": "31665146", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6821081"}, {"db": "pii", "key": "PCOMPBIOL-D-19-00529"}], "notes": [], "created": "2026-08-20T12:42:51.464Z", "modified": "2026-08-20T12:42:51.559Z"}]}