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Author Meirovitch, H. ♦ Kitson, D. H. ♦ Hagler, A. T.
Sponsorship USDOE
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword CHEMISTRY ♦ BIOLOGY AND MEDICINE, BASIC STUDIES ♦ POLYPEPTIDES ♦ ENTROPY ♦ REDUCTION ♦ COMPUTERIZED SIMULATION ♦ MATHEMATICAL MODELS
Abstract The local states (LS) method is an approximate technique proposed by Meirovitch for estimating the entropy from a sample of conformations. The method is further developed and extended here to molecular dynamics samples of the cyclic peptide cyclo-(Ala-Pro-D-Phe){sub 2} in vacuum and in the crystal environment. This is the first time the LS method has been applied to a peptide with side chains which is described by flexible geometry. The method enables one to obtain an approximation P{sub i} of the sampling probability of conformation i where P{sub i} is expressed as a product of transition probabilities, which relate to dihedral or a valence angle to a number of preceeding angles in the chain. This set of angles is called a local state. The values of P{sub i} define approximations for the entropy S (S{approximately}In P{sub i}) which together with the energy lead to upper and lower bounds for the free energy. The LS method is general; i.e., it can be applied to samples of any conformational state (e.g., a random coil) and is not restricted to a molecule undergoing small harmonic conformational fluctuations. Thus, the relative stability of states of considerable structural difference can be obtained from the corresponding free energies. In this work, the authors investigate some effects of environment on cyclo-(Ala-Pro-D-Phe){sub 2} and, in particular, calculate the reduction in entropy, {Delta}S, in going from vacuum to the crystal. They find that T{Delta}S = T[S(vacuum) - S(crystal)] = 9.4 {+-} 0.8 kcal/mol where T {approximately} 300 K is the absolute temperature. Calculations of {Delta}S is important in biological processes such as the binding of a peptide to a receptor, which involves a change of environment. It is argued that under certain conditions the method is expected to be efficient even for large proteins. 68 refs., 5 figs., 4 tabs.
ISSN 00027863
Educational Use Research
Learning Resource Type Article
Publisher Date 1992-06-17
Publisher Place United States
Journal Journal of the American Chemical Society
Volume Number 114
Issue Number 13


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