Abstract
We describe and test an implicit solvent all-atom potential for simulations of protein folding and aggregation. The potential is developed through studies of structural and thermodynamic properties of 17 peptides with diverse secondary structure. Results obtained using the final form of the potential are presented for all these peptides. The same model, with unchanged parameters, is furthermore applied to a heterodimeric coiled-coil system, a mixed α/β protein and a three-helix-bundle protein, with very good results. The computational efficiency of the potential makes it possible to investigate the free-energy landscape of these 49–67-residue systems with high statistical accuracy, using only modest computational resources by today's standards.PACS Codes: 87.14.E-, 87.15.A-, 87.15.Cc
Highlights
A molecular understanding of living systems requires modeling of the dynamics and interactions of proteins
We show that the model, in its final form, folds these different sequences to structures similar to their experimental structures, using a single set of potential parameters
We study a total of 20 peptide/protein systems, listed in Table 1
Summary
A molecular understanding of living systems requires modeling of the dynamics and interactions of proteins. Perhaps with large intrinsically disordered parts [1,2], the situation is different. When studying such proteins or conformational conversion processes like folding or amyloid aggregation, the competition between different minima on the free-energy landscape inevitably comes into focus. Studying these systems by computer simulation is a challenge, because proper sampling of all relevant free-energy minima must be ensured. This goal is very hard to achieve if explicit solvent molecules are included in the simulations. The use of coarse-grained models can alleviate this problem, but makes important geometric properties like secondary structure formation more difficult to describe
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