Computational chemistry as a helpful tool for biochemist – structure-functional study and correlation en route to protein engineering


Jan Adam1, Martina Pokorná1,  Charles Sabin2, Zdeněk Kříž1, Anne Imberty2, Jaroslav Koča1 and Michaela Wimmerová1,3



1National Centre for Biomolecular Research and 3Institute of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno  2CERMAV-CNRS, 601 rue de la Chimie, BP 53, 38041 Grenoble, France


The current computational capacity and methods allow to perform sophisticated simulations and modelling of complicated, yet, in regard to the essentials of living organisms’ existence, fundamental processes, namely biomolecular interactions. These approaches embody a great potential regarding experimental time and budget savings.

Lectins are proteins capable of binding saccharide structures with high affinity as well as high specificity. Saccharides display wide variability of conformational alternatives, being it intramolecular isomery or intermolecular linkage, and therefore able to serve as recognition agents, with lectins serving as the receptors. The interconnection of practical methods of molecular biology, structural and functional experimental methods is crucial for understanding the relationship between protein structure and its properties. The more complete this understanding, the easier and more effective the process of designing proteins with precisely defined and desired properties – protein engineering.

The study of affinity changes related to mutations of  lectin PA-IIL by combination of the aforementioned methods revealed the crucial role of the amino-acid composition of the binding site for binding preferences[1]. The studied mutants were created in silico as well, and the resulting structures were used for docking experiments. The docking results were correlated with experimental data. The aim of the project is to develop a reliable method of precognition of future, unknown interactions, both from thermodynamic and structural point of view, enabling the protein engineering approach.


[1] Adam J., Pokorná, M., Sabin, C., Mitchell, E. P., Imberty, A., and Wimmerová, M., article submitted


Acknowledgments: Supported by Grant Agency of the Czech Republic, (GA303/06/0570 and GD204/03/H016) and the Ministry of Education of the Czech Republic (MSM0021622413).