Pluripotency Conversion of Gene Studied from Quantum Folding Theory

The chemically and physically induced pluripotency in a stem cell is studied from the point of quantum transition between differentiation and pluripotency states in genes. The quantum folding theory of a macromolecule is briefly reviewed. The relation of protein folding rate with the number N of torsion modes participating in the quantum transition (coherence degree) is discussed and a simple statistical relationship is obtained. As a unifying approach to conformational quantum transition the folding rate formula can be generalized from protein to nucleic acid. It is found that the formula of folding rate versus N well fits RNA folding data. Then the quantum folding theory is applied to study the pluripotency conversion in stem cell. We proved that the acquisition of pluripotency is essentially a quantumstochastic event of small-probability through the comparison of the rate with protein folding. Due to the large coherence degree of DNA and the uphill nature of torsion transition the pluripotency-acquisition rate should be small. By establishing the reaction network of the conformational change of the pluripotency genes the characteristic time of the chemical reprogramming is calculated and the result is consistent with experiments. The dependence of the transition rate on physical factors such as temperature, PH value and the volume and shape of the coherent domain of the gene is analyzed from the rate equation. Based on these studies an approach to the physically induced pluripotency with higher rate is proposed. 1 General formula on the conformational quantum transition rate In quantum folding theory of macromolecule [1][2] the protein folding is regarded as a quantum transition between torsion states on polypeptide chain. The importance of torsion state can be looked as follows: as a multi-atom system, the conformation of a protein is fully determined by bond lengths, bond angles and torsion angles (dihedral angles), among which the torsion angles are most easily changed even at room temperature and can be assumed as the main variables of protein conformation (called as the slow variable of the system). Simultaneously, the torsion potential generally has several minima the transition between which is responsible for the conformational change. All torsion modes between contact residues are assumed to participate in the quantum transition coherently in protein . CC-BY 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/018580 doi: bioRxiv preprint first posted online Apr. 26, 2015;