Molecular modelling group
Integration of evolutive and structural information to study the function of proteins. Simulation of dynamic processes of protein-protein and protein-ligand interaction. Hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) approaches. Development of novel "in silico" drug design systems. Next-Generation Sequencing (NGS) Data Analysis.
Analysis by computational simulation of enzymatic reactions catalyzed by GTPases and ATPases of biomedical interest. Design of specific inhibitors.
Cohesin: Simulation, using molecular dynamics and QM/MM, of the ATPase activity of the active centers present in the Smc1A/Smc3 head of the human cohesin complex, involved in cell division of normal and tumor cells.
FtsZ: Simulation by molecular dynamics of the processes of polymerization and depolymerization of the bacterial septum protein FtsZ, associated with the GTPase activity of its active center.
Development of a new and efficient drug design system based on computational dynamic simulation of macromolecular structures.
Based on the analysis of Smc1A/Smc3 and FtsZ NTPasa active centers, the method developed by our group consists of simulating these protein structures through molecular dynamics for several hundred nanoseconds, selecting different representative structures and filtering a database of 3D compounds for each one of them. In both cases, notable results have been obtained:
- A molecule that inhibits the cell cycle of human tumour cells, with the potential to be used as an anti-tumour drug (in the patent study phase).
- Two bacterial cell division cycle inhibitor molecules (Escherichia coli) that can be used as potential antimicrobials (also under patent study).
In-house developed pipeline of molecular dynamics structure-based in silico strategy using databases of selected molecules to search for antimicrobial compounds ready to enter into clinical trials (e.g. carbapenemases inhibitors).
More information: http://www.cbm.csic.es/bioweb
|Last name||Name||Laboratory||Ext.*||Professional category|
|Gómez Puertas||Paulino||312||4663||pagomez(at)cbm.csic.es||E.Científicos Titulares de Organismos Públicos de Investigación|
|Marcos Alcalde||Iñigo||312||4662||imarcos(at)cbm.csic.es||Titulado Sup. Actividades Tecn. y Prof.GP1 50%|
- Marcos-Alcalde, I., Mendieta-Moreno, J.I., Puisac, B., Gil-Rodríguez, M.C., Hernández-Marcos, M., Soler-Polo, D., Ramos, F.J., Ortega, J., Pié, J., Mendieta, J. & Gómez-Puertas, P. (2017). Two-step ATP-driven opening of cohesin head. Scientific Reports 7, 3266. http://dx.doi.org/10.1038/s41598-017-03118-9
- Marcos-Alcalde, I., Setoain, J., Mendieta-Moreno, J.I., Mendieta, J. & Gómez-Puertas, P. (2015). MEPSA: minimum energy pathway analysis for energy landscapes. Bioinformatics 31, 3853-3855. http://dx.doi.org/10.1093/bioinformatics/btv453
- Mendieta-Moreno, J., Walker, R., Lewis, J., *Gómez-Puertas, P., Mendieta, J. & *Ortega, J. (*Corresponding authors) (2014). FIREBALL/AMBER: An efficient local-orbital DFT QM/MM method for biomolecular systems. Journal of Chemical Theory and Computation 10, 2185–2193. http://dx.doi.org/10.1021/ct500033w
- Martín-García, F., Mendieta-Moreno, J.I., Marcos-Alcalde, I, *Gómez-Puertas, P. & Mendieta, J. (*Corresponding author). (2013). Simulation of catalytic water activation in mitochondrial F1-ATPase using a hybrid quantum mechanics/molecular mechanics approach: An alternative role for ß-Glu 188. Biochemistry 52, 959-966. http://dx.doi.org/10.1021/bi301109x