Structural coverage of the proteome for pharmaceutical applications.

Structure-based computational drug discovery efforts have traditionally focused on the structure of a single, well-known drug target. Important applications, such as target deconvolution and the analysis of polypharmacology, require proteome-scale molecular docking and have been inaccessible to structure-based in silico approaches. One important reason for this inaccessibility was that the structure of most proteins was not known.

Understanding the fabric of protein crystals: computational classification of biological interfaces and crystal contacts.

Modern structural biology still draws the vast majority of information from crystallography, a technique where the objects being investigated are embedded in a crystal lattice. Given the complexity and variety of those objects, it becomes fundamental to computationally assess which of the interfaces in the lattice are biologically relevant and which are simply crystal contacts. Since the mid-1990s, several approaches have been applied to obtain high-accuracy classification of crystal contacts and biological protein-protein interfaces.

The environment shapes microbial enzymes: five cold-active and salt-resistant carboxylesterases from marine metagenomes.

Most of the Earth's biosphere is cold and is populated by cold-adapted microorganisms. To explore the natural enzyme diversity of these environments and identify new carboxylesterases, we have screened three marine metagenome gene libraries for esterase activity. The screens identified 23 unique active clones, from which five highly active esterases were selected for biochemical characterization.