USF Genomics
Jesper J. Madsen – PhD
Computational structural biology and the molecular basis of disease
We perform theoretical and computational scientific research in the broad fields of (bio-) physics and chemistry. Focus is directed toward the quantitative understanding on the molecular basis of biological processes pertinent to health and disease. Computer modeling and simulation are magnificent techniques for studying such structure-property relationships in unprecedented detail. Overarching research directions include:
- Development of highly efficient coarse-grained models that accurately capture the essential physics of the emergent collective behavior in biological processes.
- Using all-atom molecular dynamics simulations to study structural and dynamic changes of biological macromolecules, such cellular receptors and enzymes, in their native (often lipidic) environments.
With the insight gained from such study, we advance the understanding of complex biological phenomena on a fundamental level. The ultimate aim is to gain mechanistic insights that will lead to novel avenues for potential treatments and guide the development of drug discovery efforts.
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Publications
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Inverse Conformational Selection in Lipid-Protein Binding. A Bacle, P Buslaev, R Fandino, F Favela-Rosales, T Mendes Ferreira, P Fuchs, I Guschin, M Javanainen, A Kiirikki, JJ Madsen, J Melcr, P Milan Rodriguez, M Miettinen, OHS Ollila, C Papadopoulos, A Peon, T Piggot, A Pineiro, S Virtanen J Am Chem Soc 2021; in press.
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Uncovering Membrane-Bound Models of Coagulation Factors by Combined Experimental and Computational Approaches. YZ Ohkubo* & JJ Madsen*. Thromb Haemost 2021; in press. (*Co-corresponding author)
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Conformational Plasticity-Rigidity Axis of the Coagulation Factor VII Zymogen Elucidated by Atomistic Simulations of the N-terminally Truncated Factor VIIa Protease Domain. JJ Madsen* & OH Olsen*. Biomolecules 2021; 11(4), 549. (*Co-corresponding author)
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Tri-fluorinated Keto-Enol Tautomeric Switch in Probing Domain Rotation of a G Protein-Coupled Receptor. X Wang, W Zhao, S Al-Abdul-Wahid, Y Lu, T Cheng, JJ Madsen, L Ye. Bioconjug Chem 2021; 32(1): 99-105.
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The Potential of 19F NMR Application in GPCR Biased Drug Discovery. X Wang, A Mcfarland, JJ Madsen, E Aalo, L Ye. Trends Pharmacol Sci 2021; 42(1): 19-30.
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Cholesterol Alters the Membrane Orientation and Activity of the Influenza Virus M2 Amphipathic Helix. A Martyna, B Bahsoun, JJ Madsen, FSJS Jackson, MD Badham, GA Voth, JS Rossman. J Phys Chem B 2020; 124(31): 6738-6747.
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Water Intake and Water Molecules' Path to the Active Site of Secretory Phospholipase A2 Using MD Simulations and the Tracking Tool AQUA-DUCT. HD Tjørnelund, JJ Madsen, GH Peters. J Phys Chem B 2020; 124(10): 1881-1891.
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Efficient Simulation of Tunable Lipid Assemblies Across Scales and Resolutions. JMA Grime & JJ Madsen*. Preprint at arXiv:1910.05362 (*Corresponding author)
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Headgroup Structure and Cation Binding in Phosphatidylserine Lipid Bilayers. H Antila, P Buslaev, F Favela-Rosales, TM Ferreira, I Gushchin, M Javanainen, B Kav, JJ Madsen, J Melcr, MS Miettinen, J Määttä, R Nencini, OHS Ollila, TJ Piggot. J Phys Chem B 2019; 123(43): 9066-9079.
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Allostery in Coagulation Factor VIIa Revealed by Ensemble Refinement Analysis of Crystallographic Structures. AB Sorensen, JJ Madsen, TM Frimurer, MT Overgaard, PS Gandhi, E Persson, OH Olsen. Biophys J 2019; 116(10):1823-1835.
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Systematic Coarse-Grained Lipid Force-Fields with Semi-Explicit Solvation via Virtual Sites. AJ Pak, T Dannenhofer-Lafage, JJ Madsen, GA Voth. J Chem Theory Comput 2019; 15(3):2087-2100.
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Entropic Forces Drive Clustering and Spatial Localization of Influenza A M2 During Viral Budding. JJ Madsen, JMA Grime, JS Rossman, GA Voth. Proc Natl Acad Sci USA 2018; 115(37):E8595-E8603. Preprint at bioRxiv:291120 * Featured in U. of C. Press Release by Natalie Lund, 12 September, 2018 *
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Evolutionary Conservation of the Allosteric Activation of Factor VIIa by Tissue Factor in Lamprey: Comment. JJ Madsen, E Persson, OH Olsen. J Thromb Haemost 2018; 16: 1450-1454. Comment on Beeler et al. JTH (2018) 16(4): 734-748. Reply: Beeler et al. JTH (2018) 16(7): 1454-1456.
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Small-Angle X-ray Scattering Data in Combination with RosettaDock Improves the Docking Energy Landscape. P Sønderby, Å Rinnan, JJ Madsen, P Harris, JT Bukrinski, GH Peters. J Chem Inf Model 2017; 57:2463-2475.
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Tractors and Tractrices in Riemannian Manifolds. JJ Madsen* & S Markvorsen*. Preprint at arXiv:1707.09532 (*Co-corresponding author)
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Highly Coarse-Grained Representations of Transmembrane Proteins. JJ Madsen, AV Sinitskiy, J Li, GA Voth. J Chem Theory Comput 2017; 13:935-944.
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Acid Activation Mechanism of the Influenza A M2 Proton Channel. R Liang, JMJ Swanson, JJ Madsen, M Hong, WF DeGrado, GA Voth. Proc Natl Acad Sci USA 2016; 113:E6955-E6964.
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Theoretical Assessment of Fluorinated Phospholipids in the Design of Liposomal Drug-Delivery Systems. JJ Madsen*, P Fristrup, GH Peters*. J Phys Chem B 2016; 120:9661-9671. (*Co-corresponding author)
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Molecular Basis of Enhanced Activity in FVIIa-Trypsin Variants Conveys Insights into TF-Mediated Allosteric Regulation of FVIIa Activity. AB Sorensen, JJ Madsen, LA Svensson, AA Pedersen, H Østergaard, MT Overgaard, OH Olsen, PS Gandhi. J Biol Chem 2016; 291:4671-4683.
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Membrane Interaction of FVIIIa Discoidin Domains in Atomistic Detail. JJ Madsen, YZ Ohkubo, GH Peters, JH Faber, E Tajkhorshid, OH Olsen. Biochemistry 2015; 54:6123-6131.
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Factor VIII Interacts with the Endocytic Receptor Low-Density Lipoprotein Receptor-Related Protein 1 via an Extended Surface Comprising 'Hot-Spot' Lysine Residues. M van den Biggelaar, JJ Madsen, JH Faber, M Zuurveld, C van der Zwaan, OH Olsen, HR Stennicke, K Mertens, AB Meijer. J Biol Chem 2015; 290:16463-76. * Paper of the Week *
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Tissue Factor Activates Allosteric Networks in Factor VIIa Through Structural and Dynamic Changes. JJ Madsen, E Persson, OH Olsen. J Thromb Haemost 2015; 13:262-267. * Cover Article *
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