{"entity": "researcher", "timestamp": "2026-08-23T22:17:10.831Z", "family": "Yildirim", "given": "Ahmet", "initials": "A", "orcid": "0000-0003-1495-0288", "affiliations": ["Department of Physics, Siirt University, Siirt, Turkey."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bc5623c9a98454797e3d37cb74d3fea.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bc5623c9a98454797e3d37cb74d3fea"}}, "publications": [{"entity": "publication", "iuid": "0daf2778314e4a4bb5894dd509ccbf29", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0daf2778314e4a4bb5894dd509ccbf29.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0daf2778314e4a4bb5894dd509ccbf29"}}, "title": "Accurate absolute free energies for ligand-protein binding based on non-equilibrium approaches.", "authors": [{"family": "Gapsys", "given": "Vytautas", "initials": "V", "orcid": "0000-0002-6761-7780", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b38ff24af8447c985e97b6b0ca1c003.json"}}, {"family": "Yildirim", "given": "Ahmet", "initials": "A", "orcid": "0000-0003-1495-0288", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bc5623c9a98454797e3d37cb74d3fea.json"}}, {"family": "Aldeghi", "given": "Matteo", "initials": "M"}, {"family": "Khalak", "given": "Yuriy", "initials": "Y"}, {"family": "van der Spoel", "given": "David", "initials": "D"}, {"family": "de Groot", "given": "Bert L", "initials": "BL", "orcid": "0000-0003-3570-3534", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e7d4aedad5ac433db33e9a81991c282d.json"}}], "type": "journal article", "published": "2021-05-11", "journal": {"title": "Commun Chem", "issn": "2399-3669", "volume": "4", "issue": "1", "pages": "61", "issn-l": null}, "abstract": "The accurate calculation of the binding free energy for arbitrary ligand-protein pairs is a considerable challenge in computer-aided drug discovery. Recently, it has been demonstrated that current state-of-the-art molecular dynamics (MD) based methods are capable of making highly accurate predictions. Conventional MD-based approaches rely on the first principles of statistical mechanics and assume equilibrium sampling of the phase space. In the current work we demonstrate that accurate absolute binding free energies (ABFE) can also be obtained via theoretically rigorous non-equilibrium approaches. Our investigation of ligands binding to bromodomains and T4 lysozyme reveals that both equilibrium and non-equilibrium approaches converge to the same results. The non-equilibrium approach achieves the same level of accuracy and convergence as an equilibrium free energy perturbation (FEP) method enhanced by Hamiltonian replica exchange. We also compare uni- and bi-directional non-equilibrium approaches and demonstrate that considering the work distributions from both forward and reverse directions provides substantial accuracy gains. In summary, non-equilibrium ABFE calculations are shown to yield reliable and well-converged estimates of protein-ligand binding affinity.", "doi": "10.1038/s42004-021-00498-y", "pmid": "36697634", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9814727"}, {"db": "pii", "key": "10.1038/s42004-021-00498-y"}], "notes": [], "created": "2026-08-21T11:54:39.710Z", "modified": "2026-08-21T11:54:39.815Z"}, {"entity": "publication", "iuid": "fa6d5be7fb2b43d9924c7464fc415c68", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/fa6d5be7fb2b43d9924c7464fc415c68.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/fa6d5be7fb2b43d9924c7464fc415c68"}}, "title": "Statistical efficiency of methods for computing free energy of hydration.", "authors": [{"family": "Yildirim", "given": "Ahmet", "initials": "A", "orcid": "0000-0003-1495-0288", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bc5623c9a98454797e3d37cb74d3fea.json"}}, {"family": "Wassenaar", "given": "Tsjerk A", "initials": "TA", "orcid": "0000-0002-6345-0266", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8afd517e3cc5403e9c60829fcf6e329f.json"}}, {"family": "van der Spoel", "given": "David", "initials": "D", "orcid": "0000-0002-7659-8526", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5e69bc348284be9936c3f4ac9c6cb35.json"}}], "type": "journal article", "published": "2018-10-14", "journal": {"title": "J Chem Phys", "issn": "1089-7690", "volume": "149", "issue": "14", "pages": "144111", "issn-l": "0021-9606"}, "abstract": "The hydration free energy (HFE) is a critical property for predicting and understanding chemical and biological processes in aqueous solution. There are a number of computational methods to derive HFE, generally classified into the equilibrium or non-equilibrium methods, based on the type of calculations used. In the present study, we compute the hydration free energies of 34 small, neutral, organic molecules with experimental HFE between +2 and -16 kcal/mol. The one-sided non-equilibrium methods Jarzynski Forward (JF) and Backward (JB), the two-sided non-equilibrium methods Jarzynski mean based on the average of JF and JB, Crooks Gaussian Intersection (CGI), and the Bennett Acceptance Ratio (BAR) are compared to the estimates from the two-sided equilibrium method Multistate Bennett Acceptance Ratio (MBAR), which is considered as the reference method for HFE calculations, and experimental data from the literature. Our results show that the estimated hydration free energies from all the methods are consistent with MBAR results, and all methods provide a mean absolute error of \u223c0.8 kcal/mol and root mean square error of \u223c1 kcal for the 34 organic molecules studied. In addition, the results show that one-sided methods JF and JB result in systematic deviations that cannot be corrected entirely. The statistical efficiency \u03b5 of the different methods can be expressed as the one over the simulation time times the average variance in the HFE. From such an analysis, we conclude that \u03b5(MBAR) > \u03b5(BAR) \u2248 \u03b5(CGI) > \u03b5(JX), where JX is any of the Jarzynski methods. In other words, the non-equilibrium methods tested here for the prediction of HFE have lower computational efficiency than the MBAR method.", "doi": "10.1063/1.5041835", "pmid": "30316276", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-21T11:59:43.180Z", "modified": "2026-08-21T11:59:43.303Z"}]}