Molecular Recognition

Most cellular functions involve binding of two or more specific molecules such as proteins, nucleic acids and/or small organic molecules. In addition, most drugs work by binding to a specific target molecule and modulating its function. For example, the HIV protease inhibitors used to treat AIDS are small molecules that bind and block the function of an enzyme that the AIDS virus uses to replicate itself. The association of two specific molecules with each other, within the complex mixture of molecules that exists within the cell, is known as molecular recognition.

Because of its importance in biology and medicine, there is widespread interest in understanding what causes two molecules to bind. Moreover, the ability to design molecules that will bind to other, targeted molecules, like HIV protease, would be of enormous value in the development of new drugs, as well as in a wide range of other applications in biotechnology and chemistry.

The forces that drive binding include electrostatic attractions and the hydrophobic effect- the tendency of oily molecules to associate with each other in water. Binding is opposed by the fact that molecules constantly undergo random motions which tend to move them apart from each other, and by a number of forces, such as the tendency of water molecules to stick to charged atoms.

Molecular simulations can be used to model molecular motions under the influence of these varied forces, and thereby to predict whether two molecules will, in fact, bind to each other within the cell. The accuracy of the predictions can be assessed by comparing with experimental data from techniques such as X-ray crystallography and NMR spectroscopy, which are used in other laboratories at CARB.