6. Protein Folding

Questions addressed: Mechanisms for protein folding under the influence of external electric and electromagnetic fields? Accurate models for the description of the folding of specific proteins.  

6.1  Protein folding with and without confinement potentials (cages): 

We carried out a theoretical investigation of the folding of small proteins assisted by chaperons. We describe the proteins in the framework of an effective potential model which contains the Ramachandran angles as degrees of freedom. The cage of chaperonins is modelled by an external confining potential which is also able to take into account hydrophobic and hydrophilic effects inside the cavity. Using the Wang-Landau algorithm [Phys. Rev. Lett. 86, 2050 (2001)] we determine the density of states g(E) and analyze in detail the thermodynamical properties of the confined proteins for different sizes of the cage. We show how the confinement through the chaperon dramatically reduces the phase space available for the protein leading to a much faster folding process. Slightly hydrophobic cages seem to make the native structure more stable. However, not any confining potential helps folding. If the inner walls of the cage are strongly hydrophobic, a denaturation process is induced, in which the proteins partially unfold and stick to the walls. 

Methods: Different kinds of Monte Carlo simulations

6.2 Manipulation of proteins with electromagnetic fields

Methods: classical MD simulations, genetic algorithms, ab-initio quantum mechanical calculations.

6.3 Small proteins under external static and time-dependent electrical fields:

Methods:  MD simulations, Markov-State Modeling, Machine Learning algorithms

6.4 Simulations of the spike protein of SARS-CoV-2 under electric fields: