Some possible peculiarities of a ligand molecule binding inside of a protein macromolecule

Abstract

This article proposes a model for a ligand molecule binding inside of a protein macromolecule. The model considers peculiarities of the ligand access to a buried binding center of the protein. The number of the ligand molecule possible trajectories inside of an access channel leading to the binding center is limited by the channel. Therefore average velocity of the ligand molecule translocation inside of an access channel increase with the decreasing of its inner diameter. Thus during overcoming of the activation barrier between neighboring balanced positions inside of the channel, the ligand molecule should dissipate certain amount of its energy. In other words it should also overcome a drag barrier of activation, which is thus a component of the activation barrier. Our calculation showed that the drag barrier of activation is proportional to the temperature and to the squared ratio of the ligand diameter and the distance-averaged channel diameter. Due to possible gradient of the channel inner diameter the drag barriers of activation for the forward and backward ligand translocations inside of the channel may not equal one another. It follows from this that the binding constant depends also on the channel shape.