Libraries defining quality

It is often quite simple to build desirable physico-chemical properties into MCR-derived libraries. Defining drug-likeness in terms of log P, molecular weight, number of H-bond donors and acceptors, rotatable bonds and polar surface area, molar refractivity, MCR methodologies can produce quality drug-like hits for further optimization. 

The optimal size of the mutant library is a parameter that has immediate physical meaning. A more challenging parameter to define is the quality of the library. For example, quality can be broadly interpreted as the structural robustness or the fraction of positive mutants. The short-term goal is to produce a library that maximizes the probability of finding fitter mutants and the long-term goal is to maximize the total fitness improvement after multiple generations. Research in statistical mechanics and information theory has introduced methods that can be used to quantify the quality of a mutant library. 

According to OPCW procedures, all GC/MS runs of a sample or a blank involve the coinjection of an internal standard (hexachloroben-zene contained in the OPCW HCB mixture). This is a quality control measure, which is applied to assess the validity of the run, especially when operating in blinded mode. When AMDIS processes data from the internal standard run, it uses a small auxiliary Internal Standard Library (ASCII file onsite.isl). This library contains data on HCB (mass spectrum, RI, etc.). HCB is defined as detected if the net match factor for HCB is >80 (this is the threshold for identification, which is fixed in this version of AMDIS). Everything so far is done by AMDIS in the background. 

The selection and quality of a screening library with drug-like and lead-like structures is a critical endeavour. The features of drug-like and lead-like structures continue to be better defined, at the same time as the diversity of drug-like and lead-like molecular space continues to be explored and categorised. Other areas of development focus on the discovery of small molecules suitable for modulating protein-protein interactions, with a greater focus on natural product-like compounds. 

In the context of a GLP study (see Section 5.2) the term Study Plan or Study Protocol refers to a protocol which defines in minute detail how work is to be conducted. The Study Plan will be formally agreed by the laboratory and the client and also vetted by the quality manager (see Section 5.1). In order to avoid having to repeat descriptions of common laboratory operations in every Study Plan the GLP laboratory will maintain a library of standard operating procedures which can be cross referenced, as appropriate, in any Study Plan. 

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