Protein-shape changes affect drug binding

U.S. scientists say they have discovered protein-shape changes affect drug binding.

Computational biologists at the University of Pittsburgh School of Medicine have shown proteins have an intrinsic ability to change shape, and that allows small molecules that are attracted to a given protein to select the structure that permits the best binding.

The researchers say that premise could help in drug discovery and in designing compounds that will have the most impact on protein function to better treat a host of diseases.

Professor Ivet Bahar, who led the study, said the classical view, known as induced fit, holds that drug binding causes a change in the target protein structure. But Bahar said it now appears a protein has many different conformations that are already available.

Gathering information about the array of conformations a target protein might exhibit can be of great use when designing new drugs, Bahar said. That allows the scientist to better identify the structural pocket into which the drug must fit to cause significant alterations in protein function, such as the inhibition of an enzyme reaction.

The research by Bahar and doctoral student Ahmet Bakan appears in the early online edition of the Proceedings of the National Academy of Sciences.