Use the force

Opabinia regalis / wikimedia.org

V. Hornak, et al., "Comparison of multiple Amber force fields and development of improved protein backbone parameters," Proteins Struc Funct Bioinfo, 65:712-25, 2006. (Cited in 58 papers)

To improve a 25-year-old set of equations, called the Amber force field, which simulate the behavior of complex proteins, Carlos Simmerling, at the State University of New York at Stony Brook, tweaked the parameters that describe protein backbones in the model. The new version of Amber, dubbed "ff99SB," predicts the ways that actual proteins behave in solution.

Previous versions of Amber (published in 1999) "were too floppy," says Dave Case of Rutgers University, meaning that they overestimated spontaneous fluctuations in protein structure. "[Ff99SB] is a real quantum leap in terms of the agreement between theory and our observations" with nuclear magnetic resonance (NMR) says Rafael Brüschweiler, at Florida State University.

This year, University of Michigan researchers identified new potential for inhibiting HIV-1 protease using Amber to characterize a flexible flap in the protein. Other researchers in New York used Amber to design and synthesize new breast cancer drugs that inhibit estrogen-dependent cell growth in a mouse model.

Arthur Palmer at Columbia University says that ff99SB simulations have shown movement in tertiary loop regions of ribonuclease H protein from Escherichia coli that have been postulated but never observed. Models such as Amber, may one day be accurate enough to truly predict biomolecular behavior, says Palmer.