Systematic conformational search with constraint satisfaction
Lisa Tucker‐Kellogg, Tomás Lozano‐Pérez · 2002
The Problem: The goal of this project is to systematically enumerate feasible conformations (three-dimensional con-figurations) of a flexible molecule, subject to a given set of constraints on the distances between atoms and on the torsional angles of rotatable bonds. Without any constraints, the conformation space of a flexible molecule is astro-nomical (exponential in the number of degrees of freedom); thus, any naive, exhaustive search would be intractable. However, depending on the given set of constraints, the region of conformation space that satisfies the constraints may be small enough to search systematically. Motivation: NMR (nuclear magnetic resonance) spectroscopy experiments yield constraints on the conformations of biologically interesting molecules. For example, NMR data might provide bounds on certain interatomic distances in a protein. Our most immediate motivation is to use systematic conformational search for interpreting NMR data about a small peptide called fMLF. Solid-state NMR experiments performed by collaborators are yielding constraints on interatomic distances, torsion angles, and pairs of torsion angles for fMLF. More generally, there are many molecular modeling goals and structure determination problems that can be expressed as determining the set of structures that satisfy a given set of constraints. Previous Work: A number of systematic conformational search methods have been developed as greater computa-tional resources have become available. Pincus, Klausner & Scheraga[1] proposed a divide-and-conquer approach