Fragment-based identification of druggable 'hot spots' of proteins using Fourier domain correlation techniques.

ABSTRACT:

Motivation

The binding sites of proteins generally contain smaller regions that provide major contributions to the binding free energy and hence are the prime targets in drug design. Screening libraries of fragment-sized compounds by NMR or X-ray crystallography demonstrates that such 'hot spot' regions bind a large variety of small organic molecules, and that a relatively high 'hit rate' is predictive of target sites that are likely to bind drug-like ligands with high affinity. Our goal is to determine the 'hot spots' computationally rather than experimentally.

Results

We have developed the FTMAP algorithm that performs global search of the entire protein surface for regions that bind a number of small organic probe molecules. The search is based on the extremely efficient

SUBMITTER: Brenke R 

PROVIDER: S-EPMC2647826 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature