Myoglobin. Addition of Chemical Details to the Coarse-Grained Model Enhances Resolution of Key-Features of RMS-Fluctuation in Monte-Carlo Simulated Data and Produces Universal Distribution of Amino-Acid Content into Four Transitional Groups

Abstract

Mechanism that is driving (un)folding transitions in a protein is one of the oldest biological devices ever built by evolution. Protein is a product of a DNA-RNA-Protein line. The mechanism of (un)folding must be universal. Protein reaches very high packing density during folding. These four conditions outline our side-chain backbone based Core-Shell model. The model develops the idea that the self-assembly takes place simultaneously at two - the peptide and side-chain, backbone levels. The Sliding Mechanism of (un)folding transitions developed in the Core-Shell model states, that under unfolding conditions, the rigid-peptide plane “softens” and the side-chain backbone performs transverse discrete moves across the peptide backbone. Sliding mechanism provides a residue's stereochemistry-specific score function that places the residue in one of four distinct Transitional groups.Present work is a computational study of fluctuations of folded protein at near unfolding temperature. Our computational model of protein - a rigid-peptide plane model with Go interactions, is simple enough to allow a step-by-step addition of details. We showed earlier, that there is a reasonable qualitative agreement between NMR, X-ray and the simplified model simulated data for small proteins. Here we show that a) though the simulation data is not accurate due to the lack of chemical details in the forcefield, the rms-fluctuation profile of simplified model Myoglobin detects better all key features of conformational fluctuations of native state protein; b) the addition of Ramachandran propensities improves resolution of computational key-features. The distribution of rms-fluctuation data into four Transitional Groups obtained for amino acid content of Myoglobin is strikingly similar to the distribution of 20 amino acids into Transitional groups - a proof on universality.