About
Computational Biochemistry. Efficient Tools to fight Diseases
Location: CECAM-ES
Organisers
This is an interdisciplinary school placed in the boundaries between Chemistry and Biochemistry, or more specifically in the boundaries between Computational Chemistry and Biochemistry. The goal is to train the students in those theories and models that can be used to describe complex molecular systems by computational simulations. The subject of these simulations can be proteins, nucleic acids, membranes, carbohydrates but also all the small molecules that could interact with these entities (solvents, ions, drugs,...).The computational simulation of biological systems plays an essential role in a variety of areas, including fundamental studies of biological function and applications in biomedicine and biotechnology. Because biological processes span multiple time and space scales, biosimulations involve a variety of approaches ranging from accurate quantum chemical studies involving a reduced number of atoms to coarse grain approaches that allow simulating millions of atoms in the millisecond timescale. Indeed, often multiple descriptions are combined in so-called multiscale approaches. [1,2]
This school is focused on advanced training in the field of computational biochemistry, with particular emphasis on the applications to the study of biological processes related with human diseases at the molecular level and the development of efficient drugs. The current pandemic situation has stressed the importance of biocomputation as an efficient strategy to guide research efforts in the development of knowledge-based treatments. For this reason practical lessons will be focused on the application of bioinformatic tools to the study of SARS-CoV-2 enzymes, their function and inhibition. [3,4,5]
The school will be organized in 10 theoretical sessions, 2 hour-long each, and 5 practice sessions, 3 hour-long each. The school comprises four didactic blocks. The first block will cover an introduction to biomolecules and their properties, potential energy surfaces, the problem of the reaction coordinate in large molecular systems, Molecular Dynamics and Monte Carlo methods. The second block will focus on enhanced sampling techniques and free energy methods, and on estimating kinetic data from molecular dynamics simulation. The third block will first cover the foundations of multiscale embedding methods, including hybrid QM/MM and continuum solvation methods, and techniques to get the reaction free energy profiles in biochemical systems. Applications on biochemical reactivity will be presented based on Transition State Theory. The last block will describe the tools of ligand- based and structure-based drug design, quantitative structure-activity relationships, molecular docking and prediction of binding free energies.
All four blocks and, in particular, the practical lessons, will be oriented to applications in the biomedicine field and, more precisely, on how computer molecular simulations can assist the design of new therapeutics for diseases such as the COVID-19.
The didactic blocks will consist in the following topics:
1st Block:
Session 1. Introduction. Biomolecules and their properties. Structural databases of biomolecules. Structure-energy relationship: Biomolecules modeling (Adolfo Bastida)
Sessions 2-3. Potential energy surfaces in biomolecules. Molecular mechanics force fields. Conformational exploration. Minimization: Reaction coordinate. Molecular Dynamics and Monte Carlo methods. Structure prediction methods (Adolfo Bastida).
2nd Block:
Session 4. Enhanced sampling techniques and free energy methods 1: Umbrella Sampling & Metadynamics simulations. (Rodrigo Casasnovas).
Session 5. Enhanced sampling techniques and free energy methods 2: Replica Exchange & Accelerated Molecular Dynamics simulations. (Rodrigo Casasnovas).
Session 6. Estimation of kinetic data from molecular simulations: Kinetics from metadynamics. Markov State Models. Transition Path Sampling. (Rodrigo Casasnovas)
3rd Block:
Sessions 7-8. Models to study biochemical reactivity and applications: Continuum solvation models. Cluster models. QM/MM models; subtractive and additive schemes,. electrostatic and polarizable embedding. (Vicent Moliner & Iñaki Tuñón)
Session 9. Reaction free energy profiles in biochemical systems. Application of Transition State Theory to Biochemical reactivity (Vicent Moliner & Iñaki Tuñón)
4th Block:
Session 10. The binding process. Calculation of binding free energies. Ligand-based and structure- based drug design. Structure-activity relationships. Molecular descriptors. Quantitative structure- activity relationships (QSAR). Protein-ligand interaction. Docking techniques. (Vicent Moliner & Iñaki Tuñón)
The school will be open to European master and PhD students and postdocs with interest in the simulation of biosystems and corresponds to the level of graduate students from physical and life sciences. We will specially encourage students of the European Master in Theoretical Chemistry and Computational Modelling (EMTCCM) to attend the school, thus reinforcing the contacts among different European initiatives.
References
Vicent Moliner (Universitat Jaume I) - Organiser
Iñaki Tuñón (Universidad de Valencia) - Organiser