The Study On Protein-Peptide-Protein Three-body System Using Docking Method

Molecule docking is to evaluate the binding ability and predict the complex structure with the known 3D structures of two molecules. In many cases, a bio-molecule with lowest free energy is considered to be in a stabile state according to the thermodynamic principles. So the purpose of molecule docking is to get the conformation in the lowest free energy state.Recently, scientists has extended the range of molecule docking from protein-ligand to protein-protein or protein-peptide.This kind of research , however, almost on two body system, one receptor and one ligand: small molecule, peptide or protein. Several biologists has found some interesting features: there are many two-domain inhibitors, which could inhibit two molecules simultaneously and independently, for example, human growth hormone, hGH and its two receptors. But there is no docking program has been designed for such three-body protein-peptide system. While applying the two-body docking algorithm into the three-body system, there would be such a huge search space that the searching algorithm even can't find the global best construction ligand. Therefore, Some proper strategies have to be developed, with which we can apply the general docking program to the three-body system in certain restricted conditions or assisted means.In the first part of this dissertation, we did some research work on such protein-peptide-protein system: A two-body system program(Autodock or TPSODock)method has been extended to a reassembled three-body system such as MBTI and two Ns3 protein receptors. For this system, we have adapted general approach to exam in a two-body system to three-body system via a divide-and-conquer protocol. We developed two strategies: shielding protocol and dividing-off protocol. Both strategies are to search the global best constructions that reacted with its receptors of each active site structure free from any influences of the others.