Molecular modeling early history

Senior managers like to be able to measure the influence of a particular technique on the drug discovery pipeline, to assess the return on investment. There is no doubt that in the early days, the return on molecular modelling was mixed due to the high cost of hardware and software and the limited accuracy of the models. It is also hard to tease apart the contribution of a technique, unless an equivalent team on the same project has tried to advance without the benefit of modelling. And, as the winners get to write the history (and the chemists the patents), the true story—such as the relative opportunity costs that were saved, or incurred, by a particular strategy— is often obscured. The most effective way... 

Although the basic chemical features of coal can be qualitatively and in some instances semiquantitatively specified, average-structure models that purportedly reflect statistically preferred molecular structures of coal offer little that advances an understanding of coal. In part, this is due to a continuing paucity of relevant or reliable data and to the procedures used to formulate the constructs. But meaningful representations of molecular structure are currently also precluded by indications that the assumption that underlies average-structure models, namely, that there exists a more or less unique, systematic, rank-dependent, molecular chemistry of coal, is not sustained by the current evidence. Several examples, all drawn from the open literature, are presented to support the view that the chemistry of a coal is heavily influenced by its source materials and early formative history and that coals of similar rank may therefore be chemically much more diverse than is usually supposed. 

Dewar MJS (1989) A critique of frontier orbital theory. J Mol Struct (Theochem) 200 301-323 Doering W von E, Roth WR (1962) The overlap of two allyl radicals or a four-centered transition state in the cope rearrangement. Tetrahedron 18 67-74 Barman J (2004) Laws, symmetry, and symmetry breaking invariance, conservation principles, and objectivity. PSA 2002 Presidential Address, Philos Sci 71 1227-1241 Fisher G (2006) The autonomy of models and explanation anomalous molecular rearrangements in early twentieth-century physical organic chemistry. Stud Hist Philos Sci A 37 562-584 Gavroglu K, Simoes A (2012) Neither physics nor chemistry a history of quantum chemistry. MIT Press, Cambridge, MA... 

Turning to the behavior of typical melts, it is found that the damping function is not nearly as sensitive to molecular structure as are the linear viscoelastic properties, e.g. the storage and loss moduli. The rubberlike liquid, as well as the tube model, predict that the ratio of the first normal stress difference to the shear stress in step shear should be equal to the strain at all strains, and this is in fact observed. The other quantity measured in simple shear experiments is the second normal stress difference, but this is difficult to measure and few data are available. Of the shear histories other than step strain than have been used to study nonlinear viscoelasticity, start-up of steady simple shear has been the most used. If the shear rate is sufficiently large, some degree of chain stretch can be generated in the early stages. 

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