Hydrogen Atom Ratio-Based Docking Evolution Algorithm for the Generation of Molecular Structures

Exploring the ground-state structures of cluster molecules formed by hydrogen-bonding interactions remains a significant challenge for nanoscience. We propose a novel method called the hydrogen atom ratio-based docking evolution algorithm (HARDEA) for exploring the ground-state structures of molecules formed by hydrogen-bond interactions. This method converges faster than traditional evolutionary algorithms and has a higher probability of discovering new ground-state structures. Eighteen new ground-state structures were discovered using the HARDEA method for sulfuric acid (SA)–dimethylamine (DMA) ((SA) n (DMA) m ( n = 1–4, m = 1–4)) and sulfuric acid (SA)–3-methyl-1,2,3-butane-tricarboxylic acid (MBTCA) ((SA) n (MBTCA) m ( n = 1–3, m = 1–3)) systems and account for 67% of the total structures. The lowest-energy structures are 5.69 and 4.97 kcal/mol lower than those reported in the literature for (SA) 4 (DMA) 4 and (SA) 1 (MBTCA) 2, respectively. Compared to the field and experimental measurements of new particle formation rates, the simulated formation rates based on these new ground-state structures show improved accuracy by 20 and 3.7% than literature values for the (SA) n (DMA) m ( n = 1–4, m = 1–4) and (SA) n (MBTCA) m ( n = 1–3, m = 1–3) systems, respectively. The HARDEA method is general and flexible and can be applied to different kinds of problems with hydrogen-bond interaction, such as molecular crystal structure prediction, new particle formation, and protein–drug interactions.