Abstract: Molecular computer techniques for solving a computational problem using an array of reaction sites, for example, droplets, are disclosed. The problem may be represented as a Hamiltonian in terms of problem variables and problem parameters. The reaction sites may have a physicochemical property mapping to discrete site states corresponding to possible values of the problem variables. In a purely molecular approach, the reaction sites have intra-site and inter-site couplings enforced thereon representing the problem parameters, and the array is allowed to evolve, subjected to the enforced couplings, to a final configuration conveying a solution to the problem. In a hybrid classical-molecular approach, an iterative procedure may be performed that involves feeding read-out site states into a digital computer, determining, based on the problem parameters, perturbations to be applied to the states, and allowing the array to evolve under the perturbations to a final configuration conveying a solution to the problem.