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Algorithmic strategies in combinatorial chemistry. (English) Zbl 0963.92015

Proceedings of the 11th annual ACM-SIAM symposium on Discrete algorithms. San Francisco, CA, USA, January 9-11, 2000. Philadelphia, PA: SIAM. 275-284 (2000).
Summary: Combinatorial Chemistry is a powerful new technology in drug design and molecular recognition. It is a wet-laboratory methodology aimed at “massively parallel” screening of chemical compounds for the discovery of compounds that have a certain biological activity. The power of the method comes from the interaction between experimental design and computational modeling. Principles of “rational” drug design are used in the construction of combinatorial libraries to speed up the discovery of lead compounds with the desired biological activity.
This paper presents algorithms, software development and computational complexity analysis for problems arising in the design of combinatorial libraries for drug discovery. We provide exact polynomial time algorithms and intractability results for several Inverse Problems – formulated as (chemical) graph reconstruction problems – related to the design of combinatorial libraries. These are the first rigorous algorithmic results in the literature. We also present results provided by our combinatorial chemistry software package OCOTILLO for combinatorial peptide design using real data libraries. The package provides exact solutions for general inverse problems based on shortest-path topological indices. Our results are superior both in accuracy and computing time to the best software reports published in the literature. For 5-peptoid design, the computation is rigorously reduced to an exhaustive search of about \(2\%\) of the search space; the exact solutions are found in a few minutes.
For the entire collection see [Zbl 0933.00039].

MSC:

92C40 Biochemistry, molecular biology
92-08 Computational methods for problems pertaining to biology
05C90 Applications of graph theory
92C45 Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.)
65Y20 Complexity and performance of numerical algorithms

Software:

OCOTILLO
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