Multi-and many-objective optimization: present and future in de novo drug design.

de novo Drug Design (dnDD) aims to create new molecules that satisfy multiple conflicting objectives. Since several desired properties can be considered in the optimization process, dnDD is naturally categorized as a many-objective optimization problem (ManyOOP), where more than three objectives must be simultaneously optimized. However, a large number of objectives typically pose several challenges that affect the choice and the design of optimization methodologies. Herein, we cover the application of multi- and many-objective optimization methods, particularly those based on Evolutionary Computation and Machine Learning techniques, to enlighten their potential application in dnDD. Additionally, we comprehensively analyze how molecular properties used in the optimization process are applied as either objectives or constraints to the problem. Finally, we discuss future research in many-objective optimization for dnDD, highlighting two important possible impacts: i) its integration with the development of multi-target approaches to accelerate the discovery of innovative and more efficacious drug therapies and ii) its role as a catalyst for new developments in more fundamental and general methodological frameworks in the field.

Many-Objective Simulation-Based Optimization of an Air Separation Unit.

Air separation systems are crucial in the production of oxygen, which has gained particular relevance during the COVID-19 outbreak. Mechanical ventilation can compensate respiratory deficiencies along with the use of medical oxygen in vulnerable patients infected with this disease. In this contribution, a many-objective simulation-based optimization framework is proposed for determining eleven decision variables for the operation of an air separation unit. The framework combines the capabilities of the process simulator PRO/II with a Python environment. Three objective functions are optimized together towards the construction of a 3-D Pareto front. Results provide insightful information regarding the most adequate operating conditions of the unit, including the definition of an operational window rather than a single operational point.