Pantsar dynamics is interested in the complex dynamic interplay of pharmaceutically relevant proteins and small molecule ligands, including both protein–protein interactions and protein–ligand interactions.
We are also actively involved in understanding the role of water molecules mediating or participating in these interactions.
We utilise molecular dynamics (MD) simulations and other computer-aided drug design methods to study these interactions in the atomic scale.
Our current main research topics are:
- Ras GTPases
- Protein Kinases
Both of these protein classes are dynamic key-signalling proteins of the complex cellular signalling networks machinery. Targeting these proteins have a huge potential in treatments of distinct diseases, including cancer. There also exists already approved drugs that are in clinical use for both of these protein classes.
In Silico Evaluation of the Thr58-Associated Conserved Water with KRAS Switch-II Pocket BindersLeini, Renne; Pantsar, Tatu. 2023. Journal of chemical information and modeling. 63: 1490-1505
Decisive role of water and protein dynamics in residence time of p38α MAP kinase inhibitorsPantsar, Tatu; Kaiser, Philipp D; Kudolo, Mark; Forster, Michael; Rothbauer, Ulrich; Laufer, Stefan A. 2022. Nature communications. 13: . 569
Regulatory spine RS3 residue of protein kinases: a lipophilic bystander or a decisive element in the small-molecule kinase inhibitor binding?Shevchenko, Ekaterina; Pantsar, Tatu. 2022. Biochemical society transactions. 50: 633-648
Addressing a Trapped High-Energy Water: Design and Synthesis of Highly Potent Pyrimidoindole-Based Glycogen Synthase Kinase-3ß InhibitorsAndreev, Stanislav; Pantsar, Tatu; Tesch, Roberta; Kahlke, Niclas; El-Gokha, Ahmed; Ansideri, Francesco; Grätz, Lukas; Romasco, Jenny; Sita, Giulia; Geibel, Christian; Lämmerhofer, Michael; Tarozzi, Andrea; Knapp, Stefan; Laufer, Stefan A.; Koch, Pierre. 2021. Journal of medicinal chemistry. 2022; 65: 1283-1301
KRAS(G12C)-AMG 510 interaction dynamics revealed by all-atom molecular dynamics simulationsPantsar, Tatu. 2020. Scientific reports. 10: 11992
The current understanding of KRAS protein structure and dynamicsPantsar, Tatu. 2019. Computational and Structural Biotechnology Journal. 2020; 18: 189-198
Assessment of mutation probabilities of KRAS G12 missense mutants and their long-timescale dynamics by atomistic molecular simulations and Markov state modelingPantsar, Tatu; Rissanen, Sami; Dauch, Daniel; Laitinen, Tuomo; Vattulainen, Ilpo; Poso, Antti. 2018. PLoS computational biology. 14: e1006458