Building three-dimensional ribonucleic acid structures

orative research effort on ribonucleic acid (RNA) structure and function that started in 1987 in Robert Cedergren’s laboratory at the Université de Montréal. It involves multidisciplinary research in the fields of molecular biology, biochemistry, and computer science. The project ultimately produced MCSym, an intelligent system designed for building RNA three-dimensional (3D) structures. The RNA structure determination problem (R3D) is the search for assignments of 3D coordinates to each atom in an RNA molecule consistent with experimental or theoretical structural data when no high-resolution techniques can be applied, such as x-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy. The goal of solving R3D is to fill the gap between the number of known RNA molecules and the number of resolved structures at good resolution. R3D can be solved by using a synergetic approach between laboratory experiments and theoretical modeling. Experimental results are input to theoretical modeling, the results of which help design more precise and concise laboratory experiments. The modeling counterpart involves four steps. Step 1 consists of collecting and interpreting RNA structural data. Step 2 includes a geometrical interpretation of the accumulated structural data. Step 3 is building 3D structures, or models, that are consistent with the data prepared and formatted in Step 2. Finally, an optional Step 4 consists of refining the structures produced in Step 3 via numerical optimization methods, such as molecular mechanics and dynamics. Two of MC-Sym’s main components are the MC-Core library (http://mccore.sourceforge.net) and the MC-Sym computer program itself. MCCore is a set of C++ data structures and algorithms that store and manipulate RNA, DNA, and 3D protein structures. MC-Sym lets molecular biologists project objectively the various types and sources of RNA structural data in all-atom 3D structures (see www-lbit.iro.umontreal.ca/mcsym/). This article describes MC-Sym’s role in RNA structure determination and modeling.