Biomolecules are complex collections of atoms that dictate the chemical structure and function of life. These molecules may be as old as life itself or as recent as today is life-saving discovery of a miracle drug: molecular archeology. Their structures dictate functions, implying molecular architecture. While commercially available kits of atomic models can be used to construct models of simple molecules, the complexity of all ? or part ? of a biological macromolecule exceeds the ability of commercial kits and thus requires a novel approach. Color computer graphics is the solution of choice in the laboratory, but suffers from two severe limitations: the images are generally flat (2-dimensional) and they are ephemeral. Molecular sculptures are precise, solid molecular models which could pass for modern sculptures but also reflect the shapes and forms nature has chosen as building blocks for vital processes. They have enduring value both as images of magnificent molecules and also as plastic works of art.
Why? And How??
Discoveries on the molecular scale during the 20th century have dramatically improved our lives, improving human nutrition and health on a daily basis (vitamins, structure-based drug design). The shape and composition of a biomolecule are linked to its role in creating or sustaining life: "form follows function" or, the "structure-function relationship". Atoms and molecules are a billion (109) times too small to be seen by the eye, but we can measure them by using light (X-rays) of an equally small wavelength.
Models of molecules scaled to human dimensions have been sculpted using a computer to control a CNC milling machine. A miracle drug, a vitamin, a protein molecule and especially the sites of molecular interactions can be made to scale. For example, the amino acid cysteine (Cys) forms a dimer by bonding two sulfur atoms; this dimer helps hold protein molecules together. The S-S linkage has been sculpted in bas-relief and as freestanding models. Water molecules are an essential companion to biomolecules and have been modelled in bas-relief. Vitamins, nucleic acids, and the active sites of enzymes have been sculpted and used also for classroom teaching. Many of these examples have been taken from the results of my research laboratory at Texas A&M University. But the method is general, so other molecular models are being created in wood (oak, maple, etc.) and one day, hopefully, also in stone (marble) and other materials. The contradiction is striking - a 'blockbuster' drug can save lives and improve the health and well-being of millions, yet its chemical structure, and the beauty of the functional molecule, remains hidden. These sculptures are designed to illuminate the beauties and intricacies of the molecules of life.
First, the molecular model is positioned and scaled visually using interactive computer graphics (which I helped pioneer 30 years ago). A computer program (SCULPT) was especially written to generate the instructions for a computer numerically controlled (CNC) milling machine. The object to be sculpted ("part") is cut from solid material (e.g., wood) in two steps. These two steps are illustrated in this figure. Pass one uses lateral motion of the cutting tool to remove the empty spaces, defining the rough surface of the molecular sculpture. Pass two makes a circular cut in descending steps to define the three-dimensional surface of the atoms (or groups of atoms) which comprise the molecule or selected region of a molecule. The models can be carved to the scale of commercially available model kits, which can be used to construct drugs, ligands, or inhibitors that can be docked to the macromolecular binding site, as defied by X-ray crystallography. The standard milling machine can position the vertical cutting tool with horizontal motions. It therefore cannot carve out horizontal cavities. This is done in a two step process, "bottom-up" and "top-down", for each part or slice of the composite model. The time required to make a "part" depends on a number of factors (size, cutting speed, number of passes) but typically ranges from 2 to 4 hours per side. Program SCULPT was checked and improved and used to create about 40 sculptures last year. The program and method have broad functionality and can be augmented to create new sculpting functions. Future models will explore the ability of the method to create larger models, identify heteroatoms, and create scaled models of the active sites of enzymes, drug-receptor sites, and molecular interaction sites. Different materials are being explored (white oak, red oak, native Texan post oak, pecan, mesquite, maple, and more exotic woods) for special effects. The CNC milling machines illustrated here are used in a teaching laboratory and therefore are only available on a limited basis. They also are frequently modified for classroom projects, making it more difficult to retain standard operating parameters. However, the speed and precision of the CNC machine, and the texture and warmth of natural materials make this method attractive for the creation of sculptures of biologically significant molecular structures.
Hand-held molecular models go back 150 years and are essential for understanding molecular structures. Commercially available kits can be used to construct simple molecular models but have limited utility for macromolecules. While the casual observer will notice the fluid lines of spherical atoms assembled in space, the chemist or biologist, accustomed to studying in two dimensions from a textbook or lecture, will be challenged to relearn the shapes of amino acids, bases, vitamins. These models therefore help advance teaching and learning about molecular structures by putting them in the hands of students and scientists alike.
About the sculptor:
I am a chemist (Ph.D., University of Texas), professor (Texas A&M University), and also a X-ray crystallographer, with over 100 publications in the scientific literature. I helped pioneer interactive computer graphics(1) and was the first scientist to use color graphics for molecular modeling. I founded the Protein Data Bank(2) as a visiting scientist at the Brookhaven National Laboratory. I was the first scientist to use computer networking in the life sciences(3). My research group has determined the high-resolution structures of several proteins and enzymes that are related to nutrition, fertility, and metastatic cancer.
My first-hand contact with the intricacies of biomolecules taught me to appreciate the wonders of nature on the molecular scale. Computer graphics images, while colorful, usually are unable to convey the full, three-dimensional beauty of these molecules. I therefore developed program SCULPT(4) and a number of bas-relief and freestanding molecular sculptures.
1 Annual Report, Brookhaven National Laboratory,
1968,p. 81, E. F. Meyer; first use of color graphics for interactive molecular
2 "The First Years of the Protein Data Bank", E.F. Meyer, (1997) Protein Science 6:1591-1597
3 "A Brief History of Networking in the U.S.", E. F. Meyer and N.F. Funkhouser (1998), J.Chem.Infor.&Comp.Sci. 38:951-955.
4 "Molecular Modelling & Drug Design" Edgar F. Meyer, Stanley M. Swanson, & Jocylin A. Williams (2000), Pharmacology &Therapeutics, in the press.