Methods Applied for the Allosteric Site Revelation
Duan Ni, Shaoyong Lu, Jian Zhang · Encyclopedia of Analytical Chemistry · 2018
Abstract Allostery is the functional change at one site on a protein due to alterations at a distant site. Allosteric modulators by targeting allosteric site can fine‐tune protein's activity. Drugging allosteric sites has therefore been regarded as a novel direction in drug discovery. However, identification of allosteric sites by experimental approaches is serendipitous. Since bioinformatics and structural biology develop rapidly, protein dynamics and structures can be better understood and allosteric drug discovery is on the cusp of a novel era of rational computational methodologies. Various computational allosteric site prediction models have therefore been put forward. Computational prediction is helpful for exploration of potential allosteric sites due to its higher accuracy and relatively shorter timescale. Here, we review the state‐of‐the‐art computational allosteric sites prediction methods. We first classify different approaches according to their underlying theoretical models, then algorithms and fundamental theories behind them are revealed, and finally successful examples are presented. We put forward the current challenges faced by these approaches. Possible solutions are provided with the latest advances in the field of computational biology, and tactics to resolve these demanding tasks are also discussed.