I am interested in understanding at molecular level the function of proteins involved in hemostasis and thrombosis, and how they interact with each other and with material surfaces. My research uses mainly computational structural biology combined with experimental assays performed either by collaborators or by myself.
My research focuses on studying the structure and dynamics of proteins involved in the blood coagulation cascade in order to explain their function at atomic level of detail. One aspect of my research is understanding how oxidative stress present during inflammation alters the function, stability and binding behavior of blood coagulation factors. In particular, I study the function of von Willebrand Factor, which is essential in slowing down platelets in case of arterial injury and the self-association properties of fibrinogen, which is important to stabilize the blood clot. The main technique that I use is molecular dynamics simulations often combined with accelerated sampling methods or free energy perturbation. Since I believe that it is essential to validate computational results through experiments, I also study the behavior of von Willebrand Factor through a flow chamber assay which mimics the shear forces present in flowing blood. Oxidative stress due to traumatic injury is thought to increase the thrombotic activity of blood coagulation factors.
Biochemically, oxidation leads to the conversion of methionine residues to methionine sulfoxide. My research aims at understanding how this conversion affects the structure and function of key coagulation factors explaining their increased thrombotic activity. Insights gained onto the structural mechanism of coagulation factors can help structure based drug design to find therapeutics that can treat thrombotic diseases without causing life threatening bleeding.
Pathological blood clots can often be caused by biomedical devices implanted in the body. For this reason, I am interested in studying the interaction between proteins and material surfaces using a combination of Monte Carlo and molecular dynamics simulations. Other side projects include studying the allosteric regulation and binding properties of adhesive proteins present in bacterial fimbria.
Interlandi G, Thomas WE; Mechanism of allosteric propagation across a beta-sheet structure investigated by molecular dynamics simulations; Proteins; 84(7), 990-1008 (2016)
Rodriguez VB*, Kidd BA*, Interlandi G, Tchesnokova V, Sokurenko EV, Thomas WE; Allosteric coupling in the bacterial adhesive protein FimH; J Biol Chem, 288(33), 24128- 24139 (2013)
Liu Y, Esser L, Interlandi G, Kisiela DI, Tchesnokova V, Thomas WE, Sokurenko E, Xia D, Savarino SJ; Tight conformational coupling between the domains of the enterotoxigenic Escherichia coli fimbrial adhesin CfaE regulates binding state transition; J Biol Chem, 288(14), 9993-10001 (2013)
Interlandi G, Ling M, Tu AY, Chung DW, Thomas WE; Structural basis of type 2A von Willebrand disease investigated by molecular dynamics simulations and experiments; PLoS One; 7(10), e45207 (2012)
Yagi M, Murray J, Strand K, Blystone S, Interlandi G, Suda Y, Sobel M; Heparin modulates the conformation and signaling of platelet integrin alphaIIbbeta3; Thromb Res; 129(6), 743-749 (2012)
Baio JE, Weidner T, Interlandi G, Mendoza-Barrera C, Canavan HE, Michel R, Castner DG; Probing Albumin Adsorption onto Calcium Phosphates by XPS and ToF-SIMS; J Vac Sci Technol B Microelectron Nanometer Struct Process Meas Phenom; 29(4), 4D113 (2011)
Aprikian P*, Interlandi G*, Kidd BA, Le Trong I, Tchesnokova V, Yakovenko O, Whitfield MJ, Bullitt E, Stenkamp RE, Thomas WE, Sokurenko EV; The bacterial fimbrial tip acts as a mechanical force sensor; PLoS Biol; 9(5), e1000617
Interlandi G, Thomas W; The catch bond mechanism between von Willebrand factor and platelet surface receptors investigated by molecular dynamics simulations; Proteins; 78(11), 2506-2522 (2010)
Le Trong I, Aprikian P, Kidd BA, Forero-Shelton M, Tchesnokova V, Rajagopal P, Rodriguez V, Interlandi G, Klevit R, Vogel V, Stenkamp RE, Sokurenko EV, Thomas WE; Structural basis for mechanical force regulation of the adhesin FimH via finger trap- like beta sheet twisting; Cell; 141(4), 645-655 (2010)
Interlandi G; Backbone conformations and side chain flexibility of two somatostatin mimics investigated by molecular dynamics simulations; Proteins; 75(3), 659-670 (2009)
Interlandi G*, Wetzel SK*, Settanni G, Plückthun A, Caflisch A; Characterization and further stabilization of designed ankyrin repeat proteins by combining molecular dynamics simulations and experiments; J Mol Biol; 375(3), 837-54 (2008)
Interlandi G, Settanni G, Caflisch A; Unfolding transition state and intermediates of the tumor suppressor p16INK4a investigated by molecular dynamics simulations; Proteins; 64(1), 178-92 (2006)