| Anotace |
The aim of the project is the detailed and exhaustive mapping of the complex conformational space of short peptides and investigation of the relation between the variability of this space and protein folding. This involves the development and calibration of an efficient and robust protocol ensuring that all relevant local minima on the free energy surface of medium-sized molecules (100-200 atoms) are identified. The protocol will be based on accurate, yet efficient quantum chemical methods and an advanced solvation method, such as COSMO-RS. The full conformational space of the tripeptides composed of 20 naturally occurring amino acids (8000 systems) will then be computed, catalogued, and analysed. An extension of the system size for selected sequences (up to hexapeptides) may reveal the conformational "size-extensivity". Finally, taking a full advantage of a large and complete set of (presumably accurate) "ab initio" data we will compare them with the existing folds in proteins which may ultimately answer the fundamental question: ”How much of the protein structure is encoded in its building blocks?"
References:
1. Gutten, O.; Rulíšek, L.: Predicting the Stability Constants of Metal-Ion Complexes from First Principles. Inorg. Chem. 2013, 52, 10347‑10355.
2. Towse, C. L.; Vymetal, J.; Vondrasek, J.; Daggett, V.: Insights into Unfolded Proteins from the Intrinsic φ/ψ Propensities of the AAXAA Host-Guest Series. Biophysical Journal 2016, 110, 348‑361.
3. Ovchinnikov, S.; Kinch, L.; Park, H.; Liao, Y.; Pei, J.; Kim, D. E.; Kamisetty, H.; Grishin, N. V.; Baker, D.: Large scale determination of previously unsolved protein structures using evolutionary information. Elife 2015, 4, e09248.
4. Gutten, O.; Bím, D.; Řezáč, J.; Rulíšek, L.: Macrocycle Conformational Sampling by DFT-D3/COSMO-RS Methodology. J. Chem. Inf. Model. 2018, in press. DOI: 10.1021/acs.jcim.7b00453
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