Molecular optimization

A. N. Andriotis, N. Lathiotakis and M. Menon, Magnetic properties of Ni and Fe clusters A tight binding molecular optimization study , Chem. Phys. Lett, (in press (1996)). ... 

Combinatorial chemistry constitutes a branch of the molecular sciences, providing an array of concepts and methods to solve molecular optimization problems (in drug research and beyond) more rapidly and efficiently than classical synthetic approaches. 

Combinatorial chemistry is the branch of the molecular sciences providing concepts and methods for solving problems of molecular optimization fast and efficiently. 

The simplest form of molecular optimization to enhance pharmaceutical properties is exemplified by the modification of the antibody IgG. Because IgG constitutes a major fraction of immunoglobulin and is one of the major proteins found in plasma, it was studied with regard to pharmaceutical properties including stability, distribution. 

Molecular optimization of macromolecules often requires more research and development time. 

S. (2007) Molecular optimization using computational multi-objective methods Curr Opin Drug Discov Develop 10, 316-324. 

The REM, NK and p-spin models all are attempts to capture the important statistical properties of true molecular landscapes in a simple model. Because they contain no biophysical information, they are limited in how well they can achieve this. The block model is an important step in removing some of the simplifications in these models, as it allows for nonstationary properties that can be matched to different regions of molecules. Ideally, landscape models can be based on experimental data. Unfortunately, despite the tremendous interest in molecular optimization, there is still relatively little data that can be used this way. As more data are collected on the effects of substitutions in protein structural and loop regions, antibody CDRs and framework regions, etc., a block or other type of model can be developed that uses appropriate fitness functions for each block. Combined efforts by theoreticians and experimentalists may also help devise experiments that measure key true affinity landscape properties without excessive laboratory effort. 

DMol3 is a molecular optimization technique based on density fimctional theory quantum mechanical approach. See B. Delley, J. Chem. Phys. 92, 508 (1990), B. Delley, J. Chem. Phys. 94, 7245 (1991), B. Delley, J. Phys. Chem. 100, 6107 (1996), and B. Delley, J. Chem. Phys. 113, 7756 (2000). 

The design of enzyme inhibitors has included random screening of synthetic chemical agents, natural products, and combinatorial libraries followed by molecular optimization or structure-activity relationships of so-called lead structures as well as bio-isosteric analogues of the enzyme substrates themselves. Drugs (e.g., finasteride) also have been developed for one indication but, based on observed side effects, have lead to other uses. 

Nicolaou, C.A., Brown, N., and Pattichis, C.K. (2007) Molecular optimization using multi-objective methods. Current Opinion in Drug Discovery C Development, 10, 316-324. Brown, N. and Lewis, R.A. (2006) Exploiting QSAR methods in lead optimization. Current Opinion in Drug Discovery ej Development, 9, 419-424. 

Helgee EA, Carlsson L, Boyer S. A method for automated molecular optimization apphed to Ames mutagenicity data. J Chem Inf Model 2009 49 2559-2563. 

Molecular optimization using computational multi-objective methods. 

Shultz, M.D. (2013) Setting expectations in molecular optimizations strengths and limitations of commonly used composite parameters. Bioorganic and Medicinal Chemistry Letters, 23, 5980-5991. 

Data of primary stmcture of gene encoding PyrNPase of T. thermophilus were taken from GenBank base of nucleotides sequences. Molecular optimization of mRNA nucleotide sequence related to initial site of transcribed... 

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