{"entity": "researcher", "timestamp": "2026-08-28T00:11:23.548Z", "family": "\u00c5qvist", "given": "Johan", "initials": "J", "orcid": "0000-0003-2091-0610", "affiliations": ["Department of Cell and Molecular Biology, Uppsala University, Uppsala, 75124, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/d07d382c9c554c5faaa0a027debd2125.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/d07d382c9c554c5faaa0a027debd2125"}}, "publications": [{"entity": "publication", "iuid": "9bf4afe47da14d9ba96a54a4a3acc2a4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9bf4afe47da14d9ba96a54a4a3acc2a4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9bf4afe47da14d9ba96a54a4a3acc2a4"}}, "title": "Deciphering conformational selectivity in the A2A adenosine G protein-coupled receptor by free energy simulations.", "authors": [{"family": "Jespers", "given": "Willem", "initials": "W", "orcid": "0000-0002-4951-9220", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2d0169ec2b594e80ac6a0343a64cd4f8.json"}}, {"family": "Heitman", "given": "Laura H", "initials": "LH", "orcid": "0000-0002-1381-8464", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b7b12c4e26ad4b559d63ee100bf4cfd8.json"}}, {"family": "IJzerman", "given": "Adriaan P", "initials": "AP"}, {"family": "Sotelo", "given": "Eddy", "initials": "E"}, {"family": "van Westen", "given": "Gerard J P", "initials": "GJP"}, {"family": "\u00c5qvist", "given": "Johan", "initials": "J", "orcid": "0000-0003-2091-0610", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d07d382c9c554c5faaa0a027debd2125.json"}}, {"family": "Guti\u00e9rrez-de-Ter\u00e1n", "given": "Hugo", "initials": "H", "orcid": "0000-0003-0459-3491", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c72d19657f0e4e6a963d29ee0ab2427d.json"}}], "type": "journal article", "published": "2021-11-00", "journal": {"title": "PLoS Comput Biol", "issn": "1553-7358", "volume": "17", "issue": "11", "pages": "e1009152", "issn-l": "1553-734X"}, "abstract": "Transmembranal G Protein-Coupled Receptors (GPCRs) transduce extracellular chemical signals to the cell, via conformational change from a resting (inactive) to an active (canonically bound to a G-protein) conformation. Receptor activation is normally modulated by extracellular ligand binding, but mutations in the receptor can also shift this equilibrium by stabilizing different conformational states. In this work, we built structure-energetic relationships of receptor activation based on original thermodynamic cycles that represent the conformational equilibrium of the prototypical A2A adenosine receptor (AR). These cycles were solved with efficient free energy perturbation (FEP) protocols, allowing to distinguish the pharmacological profile of different series of A2AAR agonists with different efficacies. The modulatory effects of point mutations on the basal activity of the receptor or on ligand efficacies could also be detected. This methodology can guide GPCR ligand design with tailored pharmacological properties, or allow the identification of mutations that modulate receptor activation with potential clinical implications.", "doi": "10.1371/journal.pcbi.1009152", "pmid": "34818333", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8654218"}, {"db": "pii", "key": "PCOMPBIOL-D-21-00923"}], "notes": [], "created": "2026-08-21T12:43:46.022Z", "modified": "2026-08-21T12:43:46.114Z"}, {"entity": "publication", "iuid": "68de6424c7984f10b5e981ac5918938c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/68de6424c7984f10b5e981ac5918938c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/68de6424c7984f10b5e981ac5918938c"}}, "title": "QligFEP: an automated workflow for small molecule free energy calculations in Q.", "authors": [{"family": "Jespers", "given": "Willem", "initials": "W", "orcid": "0000-0002-4951-9220", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2d0169ec2b594e80ac6a0343a64cd4f8.json"}}, {"family": "Esguerra", "given": "Mauricio", "initials": "M", "orcid": "0000-0002-1775-586X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/beb7099f24f94eff965c1622d9ef008f.json"}}, {"family": "\u00c5qvist", "given": "Johan", "initials": "J", "orcid": "0000-0003-2091-0610", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d07d382c9c554c5faaa0a027debd2125.json"}}, {"family": "Guti\u00e9rrez-de-Ter\u00e1n", "given": "Hugo", "initials": "H", "orcid": "0000-0003-0459-3491", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c72d19657f0e4e6a963d29ee0ab2427d.json"}}], "type": "journal article", "published": "2019-04-02", "journal": {"title": "J Cheminform", "issn": "1758-2946", "volume": "11", "issue": "1", "pages": "26", "issn-l": "1758-2946"}, "abstract": "The process of ligand binding to a biological target can be represented as the equilibrium between the relevant solvated and bound states of the ligand. This which is the basis of structure-based, rigorous methods such as the estimation of relative binding affinities by free energy perturbation (FEP). Despite the growing capacity of computing power and the development of more accurate force fields, a high throughput application of FEP is currently hampered due to the need, in the current schemes, of an expert user definition of the \"alchemical\" transformations between molecules in the series explored. Here, we present QligFEP, a solution to this problem using an automated workflow for FEP calculations based on a dual topology approach. In this scheme, the starting poses of each of the two ligands, for which the relative affinity is to be calculated, are explicitly present in the MD simulations associated with the (dual topology) FEP transformation, making the perturbation pathway between the two ligands univocal. We show that this generalized method can be applied to accurately estimate solvation free energies for amino acid sidechain mimics, as well as the binding affinity shifts due to the chemical changes typical of lead optimization processes. This is illustrated in a number of protein systems extracted from other FEP studies in the literature: inhibitors of CDK2 kinase and a series of A2A adenosine G protein-coupled receptor antagonists, where the results obtained with QligFEP are in excellent agreement with experimental data. In addition, our protocol allows for scaffold hopping perturbations to identify the binding affinities between different core scaffolds, which we illustrate with a series of Chk1 kinase inhibitors. QligFEP is implemented in the open-source MD package Q, and works with the most common family of force fields: OPLS, CHARMM and AMBER.", "doi": "10.1186/s13321-019-0348-5", "pmid": "30941533", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6444553"}, {"db": "pii", "key": "10.1186/s13321-019-0348-5"}], "notes": [], "created": "2026-08-21T12:41:09.465Z", "modified": "2026-08-21T12:41:09.596Z"}]}