Distributions in protein conformation space: implications for structure prediction and entropy

Biophysical Journal
David C Sullivan, Irwin D Kuntz

Abstract

By considering how polymer structures are distributed in conformation space, we show that it is possible to quantify the difficulty of structural prediction and to provide a measure of progress for prediction calculations. The critical issue is the probability that a conformation is found within a specified distance of another conformer. We address this question by constructing a cumulative distribution function (CDF) for the average probability from observations about its limiting behavior at small displacements and numerical simulations of polyalanine chains. We can use the CDF to estimate the likelihood that a structure prediction is better than random chance. For example, the chance of randomly predicting the native backbone structure of a 150-amino-acid protein to low resolution, say within 6 A, is 10(-14). A high-resolution structural prediction, say to 2 A, is immensely more difficult (10(-57)). With additional assumptions, the CDF yields the conformational entropy of protein folding from native-state coordinate variance. Or, using values of the conformational entropy change on folding, we can estimate the native state's conformational span. For example, for a 150-mer protein, equilibrium alpha-carbon displacements in th...Continue Reading

References

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Jun 28, 2003·Biophysical Journal·David C SullivanIrwin D Kuntz

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Citations

Apr 16, 2008·Annual Review of Biochemistry·Rhiju Das, David Baker
Jun 11, 2009·The Journal of Chemical Physics·Christian L MüllerPhilippe H Hünenberger
Oct 29, 2005·Biophysical Journal·Tiba Aynechi, Irwin D Kuntz
Oct 29, 2005·Biophysical Journal·Tiba Aynechi, Irwin D Kuntz
Aug 5, 2005·Proteins·Jorge A VilaHarold A Scheraga
Aug 29, 2009·Proteins·Justin L MacCallumKen A Dill
Sep 28, 2010·Journal of Structural Biology·Michael Habeck
Mar 4, 2010·Biophysical Journal·Antonija Kuzmanic, Bojan Zagrovic
Jan 6, 2006·The Journal of Chemical Physics·Joanne M Carr, David J Wales
Oct 6, 2005·Journal of Health Communication·Robert M Wolfe, Lisa K Sharp
Mar 27, 2019·Angewandte Chemie·Alberto PerezJustin L MacCallum
Nov 21, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Razvan C StanMaristela M de Camargo
Sep 4, 2021·Frontiers in Molecular Biosciences·Kari GaalswykJustin L MacCallum
Aug 18, 2006·The Journal of Physical Chemistry. B·David C Sullivan, Carmay Lim
Jun 28, 2006·The Journal of Physical Chemistry. B·David C Sullivan, Carmay Lim

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