CompChem
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Contents |
General Information
- Application's name : Quantum Mechanical, Molecular Mechanics, and Molecular
Dynamics computation in chemistry
- Virtual Research Communities : Computational Chemistry Applications
- Scientific contact : Ivan Juranic, ijuranic@chem.bg.ac.rs
- Technical contact : Ivan Juranic, ijuranic@chem.bg.ac.rs
- Developers : Ivan Juranic, Univeristy of Belgrade, Faculty of Chemistry, Republic of Serbia
- Web site :
Application and Short Description
The project deals with modeling of molecular structure and mechanism of chemical reactions. Quantum mechanical, ab-initio, and DFT calculations will be applied for molecules that consist up to 250 atoms. Molecular mechanics and molecular dynamics simulation will be used for examination of ligands interaction with proteins and other biomacromolecules, as well as for conformational sampling of small molecules in explicit solvent cluster. In such simulations size of ligands should be up to 300 atoms; while biomacromolecule can have size of more than ten thousands of atoms. In the present stage, simulations were done by NAMD2.7.
Our research is directed toward:
a) examination of the free-energy landscapes of highly potent and very selective antitumor agents, named CSAB (see Journal of Medicinal chemistry, 48, 5600-5603, (2005); The XVI European Symposium on Quantitative Structure-Activity Relationships and Molecular Modelling, 10-17 September 2006 Mediterranean Sea / Italy. Final program& General Information pp. 274-275; and The 18th European Symposium on Quantitative Structure-Activity Relationships, 19-24 September 2010, Rhodes, Greece. Final Program & Abstract Book, pp. 278-279), in explicit solvent clusters, having different dielectric constants, H-bonding ability, and polarity, by medium lasting (~ 30ns) molecular dynamic simulations coupled with adaptive biasing force calculation;
b) Molecular dynamics simulations (~ 80 ns each) for “approach and entrance” of the group of compounds, which act as dual acetylcholine esterase (AChE) inhibitors, to enzyme active site. Whole systems (enzyme + inhibitor) for each compound are embedded in properly sized (large) solvent cluster. Last stage of each simulation includes adaptive biasing force calculation.
Several components of this approach require massive study of the vast parameter space and include tightly-coupled simulations with large memory requirements. Testing, benchmarking and production runs of some of the components can be done on standard Grid-type Linux clusters, but the core components require low-latency parallel environment. Postprocessing of trajectories, as well as output of (coupled) free-energy calculations, are also often memory demanding, so it is suitable to do such analysis on the nodes associated with the cluster where simulation were performed.
Problems Solved
Both group of compounds described in previous section are designed, synthesized and biologically tested by our group. First group of compounds represent entirely new chemotypes, as well as new chemical entities; while second group comprises new chemical entities.
Simulations described in application description under a) – CSAB – should give insight of selectivity of compounds (potency toward tumors/ toxicity toward healthy cells), which are, according to existing experimental data, highly correlated with molecular flexibility. Also, we try to find most appropriate force field among those that are available, for this type of simulation; and to examine advantages and possible disadvantages of methods of calculation used, which are relatively novel and were not applied on the systems comparable with ours, so far.
Simulations described in application description under b) – interaction of dual AChE inhibitors with the enzyme – should give insight on intramolecular interactions between the enzyme and examined compounds, and should give hint for most favorable structural modifications of compounds in order to improve their potency. To the best of our knowledge similar simulations were not reported in literature so far.
Scientific and Social Impact
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Collaborations and Beneficiaries
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Technical features and HP-SEE implementation
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Usage Example
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- Pre/post processing code : Tobefilledin
- Application tools and libraries : Enumerate (comma separated)
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- Storage space during a single run : Tobefilledin
- Long-term data storage : Tobefilledin
Publications and Presentations
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