AVB Training Program: Structural Biology
Structural Biology trainees have the opportunity to participate in projects which involve the use of x-ray crystallography, electron crystallography, multidimensional NMR, and molecular modeling. High field (9.4T, 14.1T, 17.6T) NMR spectrometers (400 MHz, 600 MHz, 750 MHz for 1H) are available to students wishing to pursue the dynamic structure of systems such as lipid-free and lipid-bound apoproteins, synthetic peptides, and oligonucleotides. Multidimensional homonuclear and heteronuclear NMR techniques are taught in conjunction with the use of distance geometry algorithms for generating three-dimensional molecular structures. Techniques for evaluating the relative probabilities of computer generated structures are taught. The trainee gains proficiency in the use of molecular modeling programs. Methods for analyzing equilibrium aspects of molecular recognition and binding are taught and applied to systems such as apo[a] kringle 9/apoB-100 fragments, lipolytic enzyme/activator complexes, and adhesion molecules/cell surface ligands. For trainees wishing to pursue static structures of biomolecules, systematic crystallization techniques are taught. When crystals of sufficient size can be grown, trainees are taught to analyze them by modern x-ray diffraction techniques. For trainees interested in proteins that are lipid-associating and not amenable to traditional crystallization methods, innovative new techniques for forming two-dimensional crystals on lipid bilayers are used. Students are also instructed in electron diffraction, cryo-electron microscopy and image analysis. In addition to formal classroom instruction, students receive practical laboratory instruction, and have access to weekly journal clubs, biweekly seminars, and periodic workshops organized by preceptors. Program faculty participating in providing instruction in these areas are listed below.