Modeling the Tertiary Structure of RNA

Abstract

INTRODUCTION
In many ways, the past decade in molecular biology could be considered the RNA decade, ushered in, as it was, by the discovery of catalytic properties associated with RNA (Cech 1983; Guerrier-Takada et al. 1983). Whereas most discoveries of this era dealt with the function of RNA (as this volume so aptly demonstrates), judging from recent trends, major developments in the next decade will concern the structure of RNA. Everything is in place: X-ray crystallography and nuclear magnetic resonance (NMR) are now applied as commonly to RNA as to proteins. Nevertheless, despite this optimistic scenario, the gap continues to grow between the number of new functional RNAs and bona fide RNA three-dimensional structures. It is to this gap that we pay homage in this review.

What Is Modeling?
Much work of the past 20–30 years has been devoted to the gathering of low-resolution data on the conformation of ribonucleic acids (McPheeters 1991). However, the full structural potential and utility of these data have often gone largely unrealized because of the inability to express them in an easily understandable format. Modern three-dimensional modeling, the process of combining, interpreting, and interpolating structural data, is the framework in which such an expression and synthesis can be made. Models serve to summarize and condense massive amounts of data into a visual, comprehensible format. The classic example of the Levitt model of tRNA is illustrative of this process (Levitt 1969). Levitt attempted to integrate the cloverleaf secondary structure, the U8.A14 base pair observed...