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Peptide Folding in Cellular Environments: A Monte Carlo and Markov Modeling Approach

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Computational Methods to Study the Structure and Dynamics of Biomolecules and Biomolecular Processes

Part of the book series: Springer Series on Bio- and Neurosystems ((SSBN,volume 8))

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Abstract

Steric interactions with surrounding macromolecules tend to favor the compact native state of a globular protein over its unfolded state. However, in experiments conducted in cells and concentrated protein solutions, both stabilization and destabilization of proteins have been observed, compared to dilute-solution conditions. Therefore, in order to understand the effects of surrounding macromolecules on protein properties such as stability, there is a need for computational modeling beyond the level of hard-sphere crowders. Here, we discuss some recent exploratory studies of peptide folding in the presence of explicit protein crowders, carried out by us using an all-atom Monte Carlo-based approach along with an implicit solvent force field. For interpreting the simulation data, time-lagged independent component analysis and Markov state modeling are used.

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Acknowledgements

The work discussed in this article was in part supported by the Swedish Research Council (Grant no. 621-2014-4522) and the Swedish strategic research program eSSENCE. The simulations were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at LUNARC, Lund University, Sweden, and Jülich Supercomputing Centre, Forschungszentrum Jülich, Germany.

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Authors and Affiliations

  1. Department of Astronomy and Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62, Lund, Sweden

    Daniel Nilsson & Anders Irbäck

  2. Institute for Advanced Simulation, Jülich Supercomputing Centre, Forschungszentrum Jülich, D-52425, Jülich, Germany

    Sandipan Mohanty

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  1. Daniel Nilsson
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Correspondence to Anders Irbäck .

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  1. Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland

    Adam Liwo

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Nilsson, D., Mohanty, S., Irbäck, A. (2019). Peptide Folding in Cellular Environments: A Monte Carlo and Markov Modeling Approach. In: Liwo, A. (eds) Computational Methods to Study the Structure and Dynamics of Biomolecules and Biomolecular Processes. Springer Series on Bio- and Neurosystems, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-319-95843-9_13

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