A graph-based genetic algorithm and generative model/Monte Carlo tree search for the exploration of chemical space

TY - JOUR

T1 - A graph-based genetic algorithm and generative model/Monte Carlo tree search for the exploration of chemical space

AU - Jensen, Jan H.

PY - 2019

Y1 - 2019

N2 - This paper presents a comparison of a graph-based genetic algorithm (GB-GA) and machine learning (ML) results for the optimization of logP values with a constraint for synthetic accessibility and shows that the GA is as good as or better than the ML approaches for this particular property. The molecules found by the GB-GA bear little resemblance to the molecules used to construct the initial mating pool, indicating that the GB-GA approach can traverse a relatively large distance in chemical space using relatively few (50) generations. The paper also introduces a new non-ML graph-based generative model (GB-GM) that can be parameterized using very small data sets and combined with a Monte Carlo tree search (MCTS) algorithm. The results are comparable to previously published results (Sci. Technol. Adv. Mater., 2017, 18, 972-976) using a recurrent neural network (RNN) generative model, and the GB-GM-based method is several orders of magnitude faster. The MCTS results seem more dependent on the composition of the training set than the GA approach for this particular property. Our results suggest that the performance of new ML-based generative models should be compared to that of more traditional, and often simpler, approaches such a GA.

AB - This paper presents a comparison of a graph-based genetic algorithm (GB-GA) and machine learning (ML) results for the optimization of logP values with a constraint for synthetic accessibility and shows that the GA is as good as or better than the ML approaches for this particular property. The molecules found by the GB-GA bear little resemblance to the molecules used to construct the initial mating pool, indicating that the GB-GA approach can traverse a relatively large distance in chemical space using relatively few (50) generations. The paper also introduces a new non-ML graph-based generative model (GB-GM) that can be parameterized using very small data sets and combined with a Monte Carlo tree search (MCTS) algorithm. The results are comparable to previously published results (Sci. Technol. Adv. Mater., 2017, 18, 972-976) using a recurrent neural network (RNN) generative model, and the GB-GM-based method is several orders of magnitude faster. The MCTS results seem more dependent on the composition of the training set than the GA approach for this particular property. Our results suggest that the performance of new ML-based generative models should be compared to that of more traditional, and often simpler, approaches such a GA.

U2 - 10.1039/c8sc05372c

DO - 10.1039/c8sc05372c

M3 - Journal article

C2 - 30996948

SN - 2041-6520

VL - 10

SP - 3567

EP - 3572

JO - Chemical Science

JF - Chemical Science

IS - 12

ER -