{"entity": "researcher", "timestamp": "2026-09-24T22:11:24.881Z", "family": "Lindahl", "given": "Viveca", "initials": "V", "orcid": "0000-0002-2679-3235", "affiliations": ["Department of Physics and Swedish e-Science Research Center, KTH Royal Institute of Technology, Stockholm, Sweden.", "Science for Life Laboratory, Stockholm and Uppsala, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/aa5ff5d55627401fbf33920c6a93c4b0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/aa5ff5d55627401fbf33920c6a93c4b0"}}, "publications": [{"entity": "publication", "iuid": "68e615c304bf4283a984616c83b5113c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/68e615c304bf4283a984616c83b5113c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/68e615c304bf4283a984616c83b5113c"}}, "title": "Permeability and ammonia selectivity in aquaporin TIP2;1: linking structure to function.", "authors": [{"family": "Lindahl", "given": "Viveca", "initials": "V", "orcid": "0000-0002-2679-3235", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/aa5ff5d55627401fbf33920c6a93c4b0.json"}}, {"family": "Gourdon", "given": "Pontus", "initials": "P"}, {"family": "Andersson", "given": "Magnus", "initials": "M"}, {"family": "Hess", "given": "Berk", "initials": "B"}], "type": "journal article", "published": "2018-02-14", "journal": {"volume": "8", "issn": "2045-2322", "issue": "1", "pages": "2995", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Aquaporin TIP2;1 is a protein channel permeable to both water and ammonia. The structural origin of ammonia selectivity remains obscure, but experiments have revealed that a double mutation renders it impermeable to ammonia without affecting water permeability. Here, we aim to reproduce and explain these observations by performing an extensive mutational study using microsecond long molecular dynamics simulations, applying the two popular force fields CHARMM36 and Amber ff99SB-ILDN. We calculate permeabilities and free energies along the channel axis for ammonia and water. For one force field, the permeability of the double mutant decreases by a factor of 2.5 for water and 4 for ammonia, increasing water selectivity by a factor of 1.6. We attribute this effect to decreased entropy of water in the pore, due to the observed increase in pore-water interactions and narrower pore. Additionally, we observe spontaneous opening and closing of the pore on the cytosolic side, which suggests a gating mechanism for the pore. Our results show that sampling methods and simulation times are sufficient to delineate even subtle effects of mutations on structure and function and to capture important long-timescale events, but also underline the importance of improving models further.", "doi": "10.1038/s41598-018-21357-2", "pmid": "29445244", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5813003"}, {"db": "pii", "key": "10.1038/s41598-018-21357-2"}], "notes": [], "created": "2018-12-05T12:48:14.107Z", "modified": "2026-09-23T11:39:33.506Z"}, {"entity": "publication", "iuid": "10b6cb74baaf4ac5abaca755f8bba4a6", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/10b6cb74baaf4ac5abaca755f8bba4a6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/10b6cb74baaf4ac5abaca755f8bba4a6"}}, "title": "Sequence dependency of canonical base pair opening in the DNA double helix.", "authors": [{"family": "Lindahl", "given": "Viveca", "initials": "V", "orcid": "0000-0002-2679-3235", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/aa5ff5d55627401fbf33920c6a93c4b0.json"}}, {"family": "Villa", "given": "Alessandra", "initials": "A"}, {"family": "Hess", "given": "Berk", "initials": "B", "orcid": "0000-0002-7498-7763", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7f8bd0772d1341ddbcd9bba2f66b042d.json"}}], "type": "journal article", "published": "2017-04-00", "journal": {"title": "PLoS Comput Biol", "issn": "1553-7358", "volume": "13", "issue": "4", "pages": "e1005463", "issn-l": "1553-734X"}, "abstract": "The flipping-out of a DNA base from the double helical structure is a key step of many cellular processes, such as DNA replication, modification and repair. Base pair opening is the first step of base flipping and the exact mechanism is still not well understood. We investigate sequence effects on base pair opening using extensive classical molecular dynamics simulations targeting the opening of 11 different canonical base pairs in two DNA sequences. Two popular biomolecular force fields are applied. To enhance sampling and calculate free energies, we bias the simulation along a simple distance coordinate using a newly developed adaptive sampling algorithm. The simulation is guided back and forth along the coordinate, allowing for multiple opening pathways. We compare the calculated free energies with those from an NMR study and check assumptions of the model used for interpreting the NMR data. Our results further show that the neighboring sequence is an important factor for the opening free energy, but also indicates that other sequence effects may play a role. All base pairs are observed to have a propensity for opening toward the major groove. The preferred opening base is cytosine for GC base pairs, while for AT there is sequence dependent competition between the two bases. For AT opening, we identify two non-canonical base pair interactions contributing to a local minimum in the free energy profile. For both AT and CG we observe long-lived interactions with water and with sodium ions at specific sites on the open base pair.", "doi": "10.1371/journal.pcbi.1005463", "pmid": "28369121", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5393899"}, {"db": "pii", "key": "PCOMPBIOL-D-16-01919"}], "notes": [], "created": "2018-12-05T11:57:46.318Z", "modified": "2026-09-23T09:26:35.333Z"}]}