Sulfuric acid (SA) together with base molecules such as ammonia (AM), methylamine (MA) and dimethylamine (DMA) is known to play a central role in atmospheric new particle formation (NPF). NPF occurs through gas-to-particle conversion via the formation and growth of molecular clusters. While previous studies have demonstrated that mixtures of bases can strongly enhance nucleation rates, the influence of multiple acidic species for larger cluster stability and growth remains less explored.</p> <p>In this work, we investigate the role of mixed-acid systems in atmospheric cluster formation using quantum chemical calculations, assisted by machine-learning. Cluster structures containing SA, methane sulfonic acid (MSA), and atmospherically relevant bases (AM, MA, and DMA), with compositions up to 10 acid–base pairs, were generated through extensive configurational sampling using ABCluster and metadynamics simulations with CREST. The resulting structures were subsequently optimized at the B97-3c level of theory, while a PaiNN machine-learning model was used to accelerate the calculation.</p> <p>Our results show that, in contrast to previously reported base synergy, the acid synergy between SA and MSA is weak and highly system dependent. SA consistently dominates the thermodynamic stability of the smallest clusters, and MSA-only acid–base interactions are insufficient to explain efficient initial particle formation. In particular, for systems involving DMA, the strong SA–DMA interaction governs the cluster energetics, with little contribution of MSA to the stability. However, MSA can influence cluster stability at larger sizes in systems involving weaker bases such as AM and MA, especially under conditions where the relative abundance of MSA is high. These findings indicate that MSA does not act as a primary nucleating acid, but rather as a secondary species that participate in the early growth of clusters.</p> <p>Overall, this work highlights that the roles of different atmospheric acids in NPF are fundamentally distinct: SA controls the initial nucleation step, whereas MSA may enhance subsequent cluster growth under specific atmospheric conditions.