A scalable approach to combinatorial library design for drug discovery.
In this paper, we propose an algorithm for the design of lead generation libraries required in combinatorial drug discovery. This algorithm addresses simultaneously the two key criteria of diversity and representativeness of compounds in the resulting library and is computationally efficient when applied to a large class of lead generation design problems. At the same time, additional constraints on experimental resources are also incorporated in the framework presented in this paper. A computationally efficient scalable algorithm is developed, where the ability of the deterministic annealing algorithm to identify clusters is exploited to truncate computations over the entire data set to computations over individual clusters. An analysis of this algorithm quantifies the tradeoff between the error due to truncation and computational effort. Results applied on test data sets corroborate the analysis and show improvement by factors as large as 10 or more, depending on the data sets.
Department of Industrial and Enterprise Systems Engineering, University of Illinois at Urbana Champaign, 104 S. Mathews Avenue, Urbana, Illinois 61801, USA. psharma2@uiuc.edu
Puneet
P
Sharma
Srinivasa
S
Salapaka
Carolyn
C
Beck
D000465:Algorithms; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008390:Markov Chains; D008956:Models, Chemical; D054852:Small Molecule Libraries; D013997:Time Factors
D054852:Small Molecule Libraries