title: Effect of hydrogen bond networks on the nucleation mechanism of protein folding.
abstract: We have recently developed a kinetic model for the nucleation mechanism of protein folding (NMPF) in terms of ternary nucleation by using the first passage time analysis. A protein was considered as a random heteropolymer consisting of hydrophobic, hydrophilic (some of which are negatively or positively ionizable), and neutral beads. The main idea of the NMPF model consisted of averaging the dihedral potential in which a selected residue is involved over all possible configurations of all neighboring residues along the protein chain. The combination of the average dihedral, effective pairwise (due to Lennard-Jones-type and electrostatic interactions), and confining (due to the polymer connectivity constraint) potentials gives rise to an overall potential around the cluster that, as a function of the distance from the cluster center, has a double-well shape. This allows one to evaluate the protein folding time. In the original NMPF model hydrogen bonding was not taken into account explicitly. To improve the NMPF model and make it more realistic, in this paper we modify our (previously developed) probabilistic hydrogen bond model and combine it with the former. Thus, a contribution due to the disruption of hydrogen bond networks around the interacting particles (cluster of native residues and residue in the protein unfolded part) appears in the overall potential field around a cluster. The modified model is applied to the folding of the same model proteins that were examined in the original model: a short protein consisting of 124 residues (roughly mimicking bovine pancreatic ribonuclease) and a long one consisting of 2500 residues (as a representative of large proteins with superlong polypeptide chains), at pH=8.3 , 7.3, and 6.3. The hydrogen bond contribution now plays a dominant role in the total potential field around the cluster (except for very short distances thereto where the repulsive energy tends to infinity). It is by an order of magnitude stronger for hydrophobic residues than for hydrophilic ones. The range of "residue-cluster" distances, at which the hydrogen bond effect exists, is twice as long for hydrophobic residues as for hydrophilic ones.
authors.affiliation: Department of Chemical and Biological Engineering, SUNY at Buffalo, Buffalo, New York 14260, USA. idjikaev@buffalo.edu
authors.forename: Y S
authors.initials: YS
authors.lastname: Djikaev
authors.forename: Eli
authors.initials: E
authors.lastname: Ruckenstein
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D011506:Proteins