Biomolecular activity basis

The Chemical Co-evolution Model was based on the assumption that every NP possessed (or had possessed at some stage in evolution) some biological activity that enhanced the fitness of the producer. This assumption is not supported by experimental evidence and the assumption has no theoretical basis. Extensive studies of collections of both synthetic chemicals and NPs have shown that the probability of any one chemical structure possessing potent, specific biological activity is very low. These experimental findings are supported by the current imderstanding of the way in which small molecules interact with proteins to bring about biomolecular activity. 

What do we know about the basis of biomolecular activity ... 

As is explained in Chapter 9, the overall classificatiom of naturally made chemicals into two classes, now commonly known as primary and secondary, first suggested by Sachs rso years ago, and subsequently defined more clearly by Kossel 50 years later, has been very rmhelpful. There are not two classes of chemicals made by plants and microbes. In Chapter 9, it is argued that some NP pathways contribute to the production of another class of substance, substances that have been selected on the basis of their physicochemical properties.5 Whereas NPs are selected on the basis of their biological activity (or more precisely their biomolecular properties, as outlined in Chapter 5), some substances made by what have traditionally been considered to be NP pathways serve as colours or as membrane components or play various other roles determined by their physicochemical properties. Hence, the NP pathways are pathways that make NPs, but these pathways are not used exclusively for this purpose. This lack of exclusivity has some interesting evolutionary implications which are discussed in Chapter 9. 

The mechanism of liver alcohol dehydrogenase (LADH) has been extensively studied. For a recent overview the reader is referred to Ref [93]. Reaction field effects on the transition structure of model hydride transfer systems have been calculated at ab initio 4-3IG basis set level [93, 94]. The active site of enzymes are usually assumed to be designed to receive molecules in the transition state for the reaction they catalyze. This special sort of surrounding medium effects has been computationally documented recently [95]. From the reaction geodesic passing through the transition state for hybride transfer in the pyridium cation/methanolate model system, only the TS-structure could be fitted into the LADH active site. The normal mode analysis carried out on the TS showed an excellent agreement with isotopic substitution experiments [95]. Reaction field calculations on this model systems have also been performed. For an overview of biomolecular interactions the reader is referred to Ref [96]. 

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