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.