{"entity": "researcher", "timestamp": "2026-09-27T15:10:11.391Z", "family": "Liao", "given": "Qinghua", "initials": "Q", "orcid": "0000-0002-2260-8493", "affiliations": ["Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University , BMC Box 596, Uppsala 75124, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/2cfe1da74631465d870b2cc2028442ab.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/2cfe1da74631465d870b2cc2028442ab"}}, "publications": [{"entity": "publication", "iuid": "cd062b7f5fa64a00baadaf78ea02f5ee", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cd062b7f5fa64a00baadaf78ea02f5ee.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cd062b7f5fa64a00baadaf78ea02f5ee"}}, "title": "Computer simulations of the catalytic mechanism of wild-type and mutant \u03b2-phosphoglucomutase.", "authors": [{"family": "Barrozo", "given": "Alexandre", "initials": "A"}, {"family": "Liao", "given": "Qinghua", "initials": "Q", "orcid": "0000-0002-2260-8493", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2cfe1da74631465d870b2cc2028442ab.json"}}, {"family": "Esguerra", "given": "Mauricio", "initials": "M", "orcid": "0000-0002-1775-586X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/beb7099f24f94eff965c1622d9ef008f.json"}}, {"family": "Marloie", "given": "Ga\u00ebl", "initials": "G"}, {"family": "Flori\u00e1n", "given": "Jan", "initials": "J", "orcid": "0000-0003-2669-4293", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d87b22cfd27b43ee89e5a7c958a6ffab.json"}}, {"family": "Williams", "given": "Nicholas H", "initials": "NH", "orcid": "0000-0002-4457-4220", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3ce19a540ded4ae2bb286e1d59c5f091.json"}}, {"family": "Kamerlin", "given": "Shina Caroline Lynn", "initials": "SCL", "orcid": "0000-0002-3190-1173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4540c85432f4cdf952b0ef7cfe1d875.json"}}], "type": "journal article", "published": "2018-03-28", "journal": {"title": "Org. Biomol. Chem.", "issn": "1477-0539", "volume": "16", "issue": "12", "pages": "2060-2073", "issn-l": "1477-0520"}, "abstract": "\u03b2-Phosphoglucomutase (\u03b2-PGM) has served as an important model system for understanding biological phosphoryl transfer. This enzyme catalyzes the isomerization of \u03b2-glucose-1-phosphate to \u03b2-glucose-6-phosphate in a two-step process proceeding via a bisphosphate intermediate. The conventionally accepted mechanism is that both steps are concerted processes involving acid-base catalysis from a nearby aspartate (D10) side chain. This argument is supported by the observation that mutation of D10 leaves the enzyme with no detectable activity. However, computational studies have suggested that a substrate-assisted mechanism is viable for many phosphotransferases. Therefore, we carried out empirical valence bond (EVB) simulations to address the plausibility of this mechanistic alternative, including its role in the abolished catalytic activity of the D10S, D10C and D10N point mutants of \u03b2-PGM. In addition, we considered both of these mechanisms when performing EVB calculations of the catalysis of the wild type (WT), H20A, H20Q, T16P, K76A, D170A and E169A/D170A protein variants. Our calculated activation free energies confirm that D10 is likely to serve as the general base/acid for the reaction catalyzed by the WT enzyme and all its variants, in which D10 is not chemically altered. Our calculations also suggest that D10 plays a dual role in structural organization and maintaining electrostatic balance in the active site. The correct positioning of this residue in a catalytically competent conformation is provided by a functionally important conformational change in this enzyme and by the extensive network of H-bonding interactions that appear to be exquisitely preorganized for the transition state stabilization.", "doi": "10.1039/c8ob00312b", "pmid": "29508879", "labels": [], "xrefs": [], "notes": [], "created": "2018-12-05T12:44:25.702Z", "modified": "2026-09-23T12:39:11.886Z"}, {"entity": "publication", "iuid": "99154b48fc8e476791294ad8cd2767ce", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/99154b48fc8e476791294ad8cd2767ce.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/99154b48fc8e476791294ad8cd2767ce"}}, "title": "Role of Ligand-Driven Conformational Changes in Enzyme Catalysis: Modeling the Reactivity of the Catalytic Cage of Triosephosphate Isomerase.", "authors": [{"family": "Kulkarni", "given": "Yashraj S", "initials": "YS"}, {"family": "Liao", "given": "Qinghua", "initials": "Q", "orcid": "0000-0002-2260-8493", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2cfe1da74631465d870b2cc2028442ab.json"}}, {"family": "Byl\u00e9hn", "given": "Fabian", "initials": "F"}, {"family": "Amyes", "given": "Tina L", "initials": "TL"}, {"family": "Richard", "given": "John P", "initials": "JP", "orcid": "0000-0002-0440-2387", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ab612d1767343bb93df821f17ee8b2a.json"}}, {"family": "Kamerlin", "given": "Shina C L", "initials": "SCL", "orcid": "0000-0002-3190-1173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4540c85432f4cdf952b0ef7cfe1d875.json"}}], "type": "journal article", "published": "2018-03-21", "journal": {"title": "Journal of the American Chemical Society", "issn": "1520-5126", "volume": "140", "issue": "11", "pages": "3854-3857", "issn-l": "0002-7863"}, "abstract": "We have previously performed empirical valence bond calculations of the kinetic activation barriers, \u0394 G\u2021calc, for the deprotonation of complexes between TIM and the whole substrate glyceraldehyde-3-phosphate (GAP, Kulkarni et al. J. Am. Chem. Soc. 2017 , 139 , 10514 - 10525 ). We now extend this work to also study the deprotonation of the substrate pieces glycolaldehyde (GA) and GA\u00b7HPi [HPi = phosphite dianion]. Our combined calculations provide activation barriers, \u0394 G\u2021calc, for the TIM-catalyzed deprotonation of GAP (12.9 \u00b1 0.8 kcal\u00b7mol-1), of the substrate piece GA (15.0 \u00b1 2.4 kcal\u00b7mol-1), and of the pieces GA\u00b7HPi (15.5 \u00b1 3.5 kcal\u00b7mol-1). The effect of bound dianion on \u0394 G\u2021calc is small (\u22642.6 kcal\u00b7mol-1), in comparison to the much larger 12.0 and 5.8 kcal\u00b7mol-1 intrinsic phosphodianion and phosphite dianion binding energy utilized to stabilize the transition states for TIM-catalyzed deprotonation of GAP and GA\u00b7HPi, respectively. This shows that the dianion binding energy is essentially fully expressed at our protein model for the Michaelis complex, where it is utilized to drive an activating change in enzyme conformation. The results represent an example of the synergistic use of results from experiments and calculations to advance our understanding of enzymatic reaction mechanisms.", "doi": "10.1021/jacs.8b00251", "pmid": "29516737", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5867644"}], "notes": [], "created": "2018-12-05T12:45:06.910Z", "modified": "2026-09-23T10:27:21.351Z"}, {"entity": "publication", "iuid": "2747281b45b74ca3a6f112138a163fe5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2747281b45b74ca3a6f112138a163fe5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2747281b45b74ca3a6f112138a163fe5"}}, "title": "Extending the Nonbonded Cationic Dummy Model to Account for Ion-Induced Dipole Interactions.", "authors": [{"family": "Liao", "given": "Qinghua", "initials": "Q", "orcid": "0000-0002-2260-8493", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2cfe1da74631465d870b2cc2028442ab.json"}}, {"family": "Pabis", "given": "Anna", "initials": "A", "orcid": "0000-0002-7705-5371", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c877704c26d477282c016a0f9186b53.json"}}, {"family": "Strodel", "given": "Birgit", "initials": "B", "orcid": "0000-0002-8734-7765", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ec7786b45b943b5bba5ac7dd42e38c1.json"}}, {"family": "Kamerlin", "given": "Shina Caroline Lynn", "initials": "SCL", "orcid": "0000-0002-3190-1173", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4540c85432f4cdf952b0ef7cfe1d875.json"}}], "type": "journal article", "published": "2017-11-02", "journal": {"title": "J Phys Chem Lett", "issn": "1948-7185", "volume": "8", "issue": "21", "pages": "5408-5414", "issn-l": "1948-7185"}, "abstract": "Modeling metalloproteins often requires classical molecular dynamics (MD) simulations in order to capture their relevant motions, which in turn necessitates reliable descriptions of the metal centers involved. One of the most successful approaches to date is provided by the \"cationic dummy model\", where the positive charge of the metal ion is transferred toward dummy particles that are bonded to the central metal ion in a predefined coordination geometry. While this approach allows for ligand exchange, and captures the correct electrostatics as demonstrated for different divalent metal ions, current dummy models neglect ion-induced dipole interactions. In the present work, we resolve this weakness by taking advantage of the recently introduced 12-6-4 type Lennard-Jones potential to include ion-induced dipole interactions. We revise our previous dummy model for Mg2+ and demonstrate that the resulting model can simultaneously reproduce the experimental solvation free energy and metal-ligand distances without the need for artificial restraints or bonds. As ion-induced dipole interactions become particularly important for highly charged metal ions, we develop dummy models for the biologically relevant ions Al3+, Fe3+, and Cr3+. Finally, the effectiveness of our new models is demonstrated in MD simulations of several diverse (and highly challenging to simulate) metalloproteins.", "doi": "10.1021/acs.jpclett.7b02358", "pmid": "29022713", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC5672556"}], "notes": [], "created": "2018-12-05T12:26:20.882Z", "modified": "2026-09-23T09:22:57.243Z"}]}