Member Tale

It took Victor Lamzin nearly a year to solve his first structure, an 800-residue enzyme formate dehydrogenase. Later, as a post-doc, he asked his supervisor to let him re-solve it, but this time in just 2 months.

Lamzin, now a group leader and the Deputy Head of the Hamburg Unit of the European Molecular Biology Laboratory, did it. “That's when I realized things could be done even quicker than that. I realized that much of the experience I had garnered and what I'd deciphered from reading the literature and talking to colleagues could be put into software,” says Lamzin. “Especially the boring, repetitive things.”

While Lamzin had scant knowledge of computer programming—in fact, he says, scant knowledge of crystallography—he dove in anyway. After all, as a scientist, learning is his job.

Lamzin's challenge led to the development of ARP/wARP. Pronounced “Arp-Warp,” the software transforms electron density maps of Xray diffraction patterns into 3-dimensional models. When ARP/wARP debuted in 1998, it was the only software of its kind. The program, written mostly in Fortran with scripting languages to support the user interface, was a collaborative effort between Lamzin's lab and that of Anastassis Perrakis of the Netherlands Cancer Institute.

“ARP/wARP, like human crystallographers, links model building and refinement together into a unified process that iteratively proceeds towards the final macromolecular model,” wrote Lamzin and Perrakis in a 2008 Nature Protocols paper describing a new release of the program. The software includes multiple, unified approaches to model building as well as ligand and solvent building components.

More recently, ARP/wARP's resolution range has expanded to allow the solution of larger structures and complexes, which have lower resolution diffraction patterns. “These structures don't always produce the Xray diffraction patterns that work best with ARP/wARP,” Lamzin says. “That means we need to develop novel methods if we want to get biologically relevant information from those structures.”

While the software still performs best at resolutions better than 2 angstroms, it can automatically solve 65% of structures at resolutions approaching 3.5 angstroms. Ultimately, Lamzin would like to solve much, much larger structures—his dream being the structure of a cell—so the software is continually under improvement.

The latest release, version 7.2, which will be available late spring 2011, contains an advanced molecular graphics front-end and an RNA/DNA builder. It integrates with CCP4 and also uses REFMAC for model refinement. For more details, visit the ARP/wARP website.

While ARP/wARP is a significant project in Lamzin's lab, his own structural biology work employs atomic resolution Xray crystallography to study the enzymatic action of proteins such as those using Nicotinamide adenine dinucleotide (NAD/NADH), the most abundant electron carrier in cell metabolism. Lamzin's work typically leads not only to publications about structural discoveries, but also to the development of technology to share. “We like to contribute with structural biology interpretations,” says Lamzin, “and at the same time with methodological advances.”

– Elizabeth Dougherty