Nitrile actsas voltmeter

Those lumpy red, white, and blue images you see in structural biology papers are meant to give a picture of how charge is distributed across a protein: Red is negative, blue is positive, and white is neutral. Such computationally derived electrostatic maps are used to identify functionally important regions-for instance, a blue trough in a DNA-binding protein hints at where nucleic acid might bind. Hoping to quantify "just how red is red, just how blue is blue," Steven G. Boxer and Ian T. Suydam of Stanford University used vibrational Stark spectroscopy and a nitrile-containing inhibitor to experimentally test electrostatic calculations for human aldose reductase, a well-characterized diabetes drug target (Science 2006, 313, 200). Upon mutation of the enzyme's active site, they observed changes in the nitrile's vibrational frequency that can be used to quantify the local electric field. Using these data as a benchmark, they worked with Vijay S. Pande's group to show that using long-term molecular dynamics simulations greatly improves the accuracy of electrostatic calculations. The technique can be readily generalized and could find wide use for verifying protein electrostatics calculations, Boxer says.