PNNL

Abstract

Even a relatively small molecule with 10–20 atoms might have a few local minima, which correspond to different conformers. The number of local minima quickly increases with molecular size and the most common algorithms, driven by calculated forces, frequently identify a minimum, which is closest to the initial structure, rather than the most stable conformer. Here we discuss how to perform a systematic search of the conformational space for a chain-like molecule. Our approach is fully automated and a user has control which chemical bonds will be probed and with which increments. Moreover, whole fragments of the molecule, which are adjacent to each selected rotational bond, are rotated in a properly selected cylindrical coordinate system and unchemical hybridizations and some ‘‘clashes’’ between neighboring groups, which are common when standard Z-matrices are used, are avoided. A library of potentially relevant conformers is created with a tool, which we call SSC, denoting Systematic Screening of Conformers. Each member of the library is prescreened at a predefined level of theory and the most promising conformers are identified. Finally, they are further evaluated at a higher level of theory to identify the most stable structures and their physicochemical properties. As an example, we demonstrate the results of this approach for 2'-deoxycytidine.