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Statistical-mechanical lattice models for protein-DNA binding in chromatin
Statistical-mechanical lattice models for protein-DNA binding are well
established as a method to describe complex ligand binding equilibriums
measured in vitro with purified DNA and protein components. Recently, a new
field of applications has opened up for this approach since it has become
possible to experimentally quantify genome-wide protein occupancies in relation
to the DNA sequence. In particular, the organization of the eukaryotic genome
by histone proteins into a nucleoprotein complex termed chromatin has been
recognized as a key parameter that controls the access of transcription factors
to the DNA sequence. New approaches have to be developed to derive statistical
mechanical lattice descriptions of chromatin-associated protein-DNA
interactions. Here, we present the theoretical framework for lattice models of
histone-DNA interactions in chromatin and investigate the (competitive) DNA
binding of other chromosomal proteins and transcription factors. The results
have a number of applications for quantitative models for the regulation of
gene expression.Comment: 19 pages, 7 figures, accepted author manuscript, to appear in J.
Phys.: Cond. Mat
Monte Carlo study of cooperativity in homopolypeptides
©1992 American Institute of PhysicsThe electronic version of this article is the complete one and can be found online at: http://link.aip.org/link/?JCPSA6/97/9412/1DOI:10.1063/1.463317A discretized model of globular proteins is employed in a Monte Carlo study of the helix-coil transition of polyalanine and the collapse transition of polyvaline. The present lattice realization permits real protein crystal structures to be represented at the level of 1 A resolution. Furthermore, the Monte Carlo dynamic scheme is capable of moving elements of assembled secondary and supersecondary structure. The potentials of mean force for the interactions are constructed from the statistics of a set of high resolution x-ray structures of nonhomologous proteins. The cooperativity of formation of ordered structures is found to be larger when the major contributions to the conformational energy of the low temperature states come from hydrogen bonds and short range conformational propensities. The secondary structure seen in the folded state is the result of an interplay between the short and long range interactions. Compactness itself, driven by long range, nonspecific interactions, seems to be insufficient to generate any appreciable secondary structure. A detailed examination of the dynamics of highly helical model proteins demonstrates that all elements of secondary structure are mobile in the present algorithm, and thus the folding pathways do not depend on the use of a lattice approximation. Possible applications of the present model to the prediction of protein 3D structures are briefly discussed
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