Conformability Analysis application modes

Kolossvary I and W C Guida 1996 Low Mode Search An Efficient, Automated Computational Method for Conformational Analysis- Application to Cyclic and Acyclic Alkanes and Cyclic Peptides Journal of the American Chemical Society 118 5011-5019. 

Molecular mechanics calculations are an attempt to understand the physical properties of molecular systems based upon an assumed knowledge of the way in which the energy of such systems varies as a function of the coordinates of the component atoms. While this term is most closely associated with the conformational energy analyses of small organic molecules pioneered by Allinger (1), in their more general applications molecular mechanics calculations include energy minimization studies, normal mode calculations, molecular dynamics (MD) and Monte Carlo simulations, reaction path analysis, and a number of related techniques (2). Molecular mechanics... 

An application of the ROCS program has been reported recently (82). New scaffolds for small molecule inhibitors of the ZipA-FtsZ protein-protein interaction have been found. The shape comparisons are made relative to the bioactive conformation of a HTS hit, determined by X-ray crystallography. A followup X-ray crystallographic analysis also showed that ROCS accurately predicted the binding mode of the inhibitor. This result offers the first experimental evidence that validates the use of ROCS for scaffold hopping purposes. 

Modern vibrational spectroscopy of polypeptides and proteins, as outlined in the previous pages, has made a significant initial contribution as a tool for the detailed analysis of conformation in such molecules. Yet much more remains to be done, both with respect to further refinements in the inputs to the normal-mode calculations as well as in applications to the many general and specific structures that need to be studied. We consider below only briefly some aspects of such future developments. 

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