Modeling biologically important molecules and their complexes (2204)

Dr. sc. Antonija Tomić, Research Associate

Ruđer Boskovic Institute

Understand the methods and techniques used in modelling molecules and their complexes and know
possibilities of molecular modeling to solve specific problems in biosciences as well as in the planning and execution of experiments.

With the development of computers and computer programs, and the decline in their price, molecular modeling has found its wide application in almost all biosciences. This relatively new scientific discipline has developed rapidly in the last decade and has become popular among biophysicists, biochemists, biologists and medics.
During the course, students will get acquainted with the basic assumptions and methods of molecular modeling. Starting with getting to know the databases we use in biomacromolecules modeling, through insights into modeling techniques and force fields used in modeling biomacromolecules and their complexes, participants will learn how to design a virtual (in silico) experiment that will serve as a real one for them. The topics of the lecture will be adapted to the knowledge and needs of students, and will certainly include: the design of protein mutants, the construction of a complex of proteins and nucleic acids with small molecules, and the macro.molecules themselves, finding an active place and placing the substrate in that place, parameterizing and optimizing structures (systems), possible changes in shapes (receptors, ligands, complexes) that occur during binding and how to model them.
Participants will get acquainted with the basic characteristics of quantum mechanical and empirical methods and their importance in modeling biological molecules and processes. They will learn how to model enzymatic reactions on real systems (without using approximative, small models) using hybrid qvantly mechanical and iempirical methods (QM/MM and QM/MD). Through an overview of practical approaches to problems, methods of molecular mechanics and dynamics, Monte Carlo, and analysis of normal modes will be processed. The significance of solvents and periodicity in biological molecules and the assessment of rotational/conformation entropy will be explained. On concrete examples, students will get acquainted with the techniques used in finding a quantitative relationship on the structure of dependent sizes with biological activity.

Particular attention will be paid to the interpretation of the model, i.e. how to draw relevant conclusions from the obtained modeling results and on the basis of them set up (i.e. explain) the actual experiment.

1. Apply molecular modeling methods and abbreviations that are frequently used in scientific papers, related to molecular modeling (MD, QM, QM/MM, QSAR, PCA, NM, SAS...)
2. Explain the concept of force fields most commonly used in the modelling of biological macromolecules as well as the basic characteristics of these force fields.
3. Assess the importance of solvents in molecular modeling.
4. Compare different hybrid quantum-mechanical and molecular mechanical methods.
5. Explain the basics of thermodynamics and statistical physics.

Regular attendance with possible justified absence of up to 5 hours of classes and 3 hours of exercises

We will conduct a check on the ability to use existing programs for molecular modeling.

Essentials of Computational Chemistry, C.J. Cramer, John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester,West Sussex PO19 8SQ, England, 2004

Computational structural biology : T. Schwede, Torsten, World Scientific, 2008
Molecular modelling of Proteins, A. Kukol, Humana Press, 2008.

Question marks before and after classes, talking to students and colleagues about possible new topics and about the extensiveness of access to different teaching units.
The success of the course will be evaluated annually by the joint expert committee of the Rudjer Boskovic Institute, the University of Dubrovnik and the University of Osijek