Energy-directed tree search:an efficient systematic algorithm for finding the lowest energy conformation of molecules

摘要

We present a new systematic algorithm,energy-directed tree search (EDTS),for exploring the conformational space of molecules.The algorithm has been designed to reliably locate the global minimum (or,in the worst case,a structure within 4 kJ mol~(-1) of this species) at a fraction of the cost of a full conformational search,and in this way extend the range of chemical systems for which accurate thermochemistry can be studied.The algorithm is inspired by the build-up approach but is performed on the original molecule as a whole,and objectively determines the combinations of torsional angles to optimise using a learning process.The algorithm was tested for a set of 22 large molecules,including open- and closed-shell species,stable structures and transition structures,and neutral and charged species,incorporating a range of functional groups (such as phenyl rings,esters,thioesters and phosphines),and covering polymers,peptides,drugs,and natural products.For most of the species studied the global minimum energy structure was obtained;for the rest the EDTS algorithm found conformations whose total electronic energies are within chemical accuracy from the true global minima.When the conformational space is searched at a resolution of 120°,the cost of the EDTS algorithm (in its worst-case scenario) scales as 2~N for large N (where N is the number of rotatable bonds),compared with 3~N for the corresponding systematic search.