Detailed study of interactions between small molecules and proteins using molecular modeling

Z. Kříž1, M. Otyepka2, I. Bártová1, J. Koča1


1National Centre for Biomolecular Reserach, Faculty of Scinece, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic.

2Department of Physical Chemistry, Faculty of Science, Palacký University, Tř. Svobody 8, 771 46 Olomouc, Czech Republic.


Detailed knowledge of interactions inside the proteins plays an important role in drug design.    Experimental methods such as X-crystallography, NMR spectroscopy and neutron diffraction are typical experimental methods to analyze these interactions at atomic level [1]. These experimental methods can, in some cases, be complemented by molecular modeling methods. The molecular docking combined with flexible conformational search, molecular dynamics and quantum dynamics are the most used modeling methods at this time.


Recently, the interactions of solvent molecules with cyclin dependent kinase (CDK2) using molecular dynamics were studied in our laboratory [2]. The study was extended to molecular dynamics with mixtured solvent (water molecules mixtured with small organic molecules) and also to utilization of systematic molecular docking of small organic molecules into CDK2 using CICADA [3, 4] program. The results of such calculations will be used. As a mixtured solvent water + dimethylether and water + methylamine were used. The results will be compared with systematic docking search combined with molecular dynamics  and also steered molecular dynamics method.


This work was supported by grant LN00A016 of the Ministry of Education, Youth and Sports of the Czech republic.





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