Receptor-based design techniques use information about the structure of a drug target (receptor) as a basis for the design of lead compounds. This includes applications to address critical receptor-based design tasks, such as ligand docking, virtual screening, lead optimization.

From humble beginnings by great Austrian and British scientists such as Perutz and Kendrew, protein structure determination has become a major scientific and commercial enterprise. With the genome as a road map protein structures are solved faster and more routinely than ever before. The primary purpose of having the three dimensional coordinates of a protein, or protein complex, is to elucidate mode of action. How do proteins do what they do, and how can we affect what it is they do? It has been a common, and often incorrect, tenet that given the structure function will be obvious. And indeed broad but useful characterizations can often be made: a DNA binding protein will have a decidedly positive electrostatic area around the binding side, an enzyme will typically have a deep, water inaccessible pocket. However, the detailed description of mechanism is rarely revealed, largely because of weakness in our understanding of the physics of solvation and electrostatics. Proteins are very complex systems, even when they look simple.

OpenEye is contributing both scientifically and with software to this burgeoning field, from crystallography to physical property calculation to ligand docking. Our approach is to apply the same technologies to proteins that have been so successfully applied to the small molecule world. Shape and electrostatics are even more important to the understanding of proteins than they are the behavior of the ligands that bind to them.

FRED- extremely fast, systematic docking search for ligand binding within a protein active site

A docking program that fits molecules into the active site of a protein based primarily on shape complementarity. Gaussian shape functions are used to define the interaction of protein and ligand, which results in a huge advantage in performance. So much so that all poses (rotations and translations) within a given tolerance can be examined in less time than stochastic or rule-based methods (typically, single conformers in milliseconds). Although FRED can use ligand information (allowing constraints to be applied to chemical functionalities), it works primarily as a fast screening tool for Large Scale Virtual Screening.

Seascape Scientific Partner:OpenEye Scientific Software, New Mexico

AFITT- crystallographic refinement and analysis

AFITT, a crystallographic offering, allows visualization and manipulation of protein structure and electron density. It features novel, real-space refinement of both ligands and side-chains with the MMFF force-field, easy access to commonly available packages and facile handling of ligand chemistry. Available on many platforms.

Seascape Scientific Partner:OpenEye Scientific Software, New Mexico

QUACPAC- quality charge states and charges for small molecules and proteins

In addition to providing methods of applying partial charges to proteins, the protein_pka module can estimate both charge states and tautomer preferences both for apo and ligand complexed proteins. Based on the ZAP toolkit, OEChem and MMFF, protein_pka is essential software for correct protein physics.

Seascape Scientific Partner:OpenEye Scientific Software, New Mexico

VIDA II - molecular visualization and data analysis on very large datasets

Protein visualization is an important aspect of structural biology. VIDA II offers PB electrostatics, secondary structure depiction, surface rendering and selection, proximity analysis, electron density visualization, split view and multi-paned views, stereo and high-quality image construction all in a simple, multi-platform package.

Seascape Scientific Partner:OpenEye Scientific Software, New Mexico





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