Abstract
A generic coarse-grained (CG) protein model is presented. The intermediate level of resolution (four beads per amino acid, implicit solvent) allows for accurate sampling of local conformations. It relies on simple interactions that emphasize structure, such as hydrogen bonds and hydrophobicity. Realistic alpha/beta content is achieved by including an effective nearest-neighbor dipolar interaction. Parameters are tuned to reproduce both local conformations and tertiary structures. The thermodynamics and kinetics of a three-helix bundle are studied. We check that the CG model is able to fold proteins with tertiary structures and amino acid sequences different from the one used for parameter tuning. By studying both helical and extended conformations we make sure the force field is not biased toward any particular secondary structure. The accuracy involved in folding not only the test protein but also other ones show strong evidence for amino acid cooperativity embedded in the model. Without any further adjustments or bias a realistic oligopeptide aggregation scenario is observed.
Highlights
Proteins are the building blocks of biology
Our model has proven very efficient in finding the equilibrium conformation of various helical structures, up to small deviations, and independent of their tertiary structurei.e., number of helicesor sequence of amino acids
Since the simulation temperature of Gsponer et al in our case maps to T = 1E / kB, which is where we essentially find the phase transitionFig. 11͒, effects only captured by the atomistic force field can be expected to lead to substantial differences
Summary
Proteins are the building blocks of biology. They are evolutionarily optimized heteropolymers, whose physical and material properties more often than not exceed what can be readily understood from conventional polymer physics reasoning, which derives much of its strength from uniformity, randomness, and the law of large numbers. Off-lattice simulations were developed using one bead per amino acid with implicit solvent; famous examples are Gō models.[15] This level of resolution allows for much more conformational freedom, which is key to structural studies. Intermediate level resolution models have shown promising results in capturing local conformations and reproducing basic aspects of secondary structure recognition while gaining much computational efficiency compared to atomistic models. This is partly due to the removal of solvent, which allows for significant speedup, as water typically represents the bulk of a simulation in such systems. The paper is divided into several parts: the mapping scheme will explain how atomistic details were coarsegrainedCGout, the different interactions as well as parameter tuning and simulation methods will be described, and several applications will show to what extent the model can reproduce structural properties
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