Simulations Of Interaction Between Polymer With Small Molecules And Protein-Ligand Binding Dynamics

The interaction between biomacromolecules and other molecules in theenvironment, containing non-bonded interaction and chemical reaction, plays a verysignificant role in the conformational stability, solubility and chemical properties ofthe macromolecules. We focus on these two kind interactions by means of dynamicssimulations. For the former, ambient conditions as temperature and ions conditionare considered and for the later, the dynamics process is the focus.The hydrogen bonding interaction is the main part of interactions betweenhydrogen bond dominated macromolecules and other molecules. Its effect on theconformational stability and solubility of macromolecules is investigated by takingthe interaction of cellulose and urea in urea/alkali solvent mixture as an emample.The results display an inclusion complex is formed between them and itstemperature properties. We also find there is only one dominative hydrogen bondingpattern which proves the conjugated bond in urea should be the driving force for theinclusion complex. These finding is very helpful to understand the mechanism ofdissolution of cellulose in urea/alkali solvent mixture and the role that urea playsduring the process.The other part of non-bonded interaction is electrostatic interaction. TheG-quadruplex formed by thrombin-binding aptamer (TBA) with Mg2+existing isstudied in the section three. A force is added to this system which allows us to studythe electrostatic interaction between DNA aptamer and metal ions by MolecularDynamics simulations. The results show the electrostatic interaction between TBAand Mg2+is strong, however, when there are K+ions around them, it becomes weaker.With the function of the additional force, the G-quadruplex structures with differentmetal ions around them display different unfolding ways.For chemical reaction, we focus on the dynamics process of it. The kinetics ofprotein-ligand binding coupled to conformational change is studied by BrownianDynamics simulations in the Section four. During the simulation,dual-transition-rates model from Zhou is used, and is made more realistic byrestricting the reactive region to a patch. The simulation results show that, for anenergy surface that switches from favoring the nonreactive conformation while theligand is away to favoring the reactive conformation while the ligand is near, the slow limit and fast limit of binding rate constants become close and, thus, providetight bounds to the binding rate constant. They are in excellent agreement with theanalytical theory from Zhou.Receptor-binding rate constants of disordered ligands and the protein linkedwith a flexible linker are also investigate by means of Brownian Dynamics inSection five. In the simulation model, we consider the flexible linker of the proteinas a worm-like chain and find that the binding rate constant of the disordered ligandscould reach a maximum by changing the linker contour length or flexibility.