Conformation Redundancy

The parameter redundancy is also the reason that care should be exercised when trying to decompose energy differences into individual terms. Although it may be possible to rationalize the preference of one conformation over another by for example increased steric repulsion between certain atom pairs, this is intimately related to the chosen functional form for the non-bonded energy, and the balance between this and the angle bend/torsional terms. The rotational banier in ethane, for example, may be reproduced solely by an HCCH torsional energy term, solely by an H-H van der Waals repulsion or solely by H-H electrostatic repulsion. Different force fields will have (slightly) different balances of these terms, and while one force field may contribute a conformational difference primarily to steric interactions, another may have the... 

Average occurrence in more than 1,150 proteins. From Doolittle, R.F (1989) Redundancies in protein sequences. In Prediction of Protein Stricture and the Principles of Protein Conformation (Fasman, G.D., ed.), pp. 599-623, Plenum Press, New York. 

A common difficulty accompanying the representation of the conformational space by sampling is the redundancy among conformers. Usually many hundreds or thousands of conformers are generated and then reprocessed to pick out families representative of the whole space. After a local minimization, many of these conformers may fall into the same conformation, reproduced several times. Therefore, Catalyst focuses on the coverage of all possible bioactive conformations of a compound compared with methods that represent conformational space as a collection (clusters) of local minima. 

The molecule preparation step includes also conformational expansion using a torsional search or a combined Monte Carlo Multiple Minimum/Low Mode search. During the search, the intramolecular hydrogen bonds are not considered. Molecules can be minimized, OPLS-2005 or MMFF force fields [86, 87] are available, and also two continuum solvation models (distance-dependent dielectric or GB/SA). A double criterion is used to eliminate redundant conformations it uses distances between pairs of corresponding atoms within a 1 kcal moh1 energy window. 

The PPR has also implications in conjunction with the thermodynamic hypothesis [86,87], the Levinthal paradox [88], the use of redundant conformations in conformational searches, and the possibility of an enhanced search procedure (projected angle method). These points lie outside the scope of the present work and will be discussed in detail in future work [89]. 

As long as one knows that these parameters refer to an established conformation, the disordered chain, this redundancy or pseudocomplex description is innocuous, and it does permit a direct comparison of coefficients charac-acterizing the disordered and helical conformations by virtue of a mathematical form common to both. If bo has a value other than zero, then taking the difference between [m ]f and given respectively by Eqs. 

All of the material has been organized to eliminate redundancy. A chapter on molecular endocrinology has been added, the molecular biology section has been updated, many of the figures have been redrawn, and the questions have been revised, not only to conform with the USMLE style but also to reflect the current emphasis on clinical problem solving. 

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