Title: "Conformational Entropy of Polypeptides: Flory's Isolated-Pair Hypothesis and Energy Decomposition"
Speaker: Dr. Y. Zenmei Ohkubo, Department of Molecular Biology, The Scripps Research Institute, La Jolla CA
Place: Stanley Coulter (SC) 239; September 28, 2004, Tuesday, 4:30pm


We are using various molecular dynamics methods to elucidate protein folding characteristics that are difficult to capture experimentally. To evaluate Flory's isolated-pair hypothesis, we explore equilibrium conformations of alpha-helix-forming Ac-ALA_n-NMe and the C-peptide homologues as a function of temperature by means of replica exchange molecular dynamics (REMD) in conjunction with the CHARMM/GB implicit solvent force field and the weighted histogram analysis method (WHAM). We also compute Zimm-Bragg parameters, s and sigma, of Ac-ALA_n-NMe. The obtained s(T) and sigma(T) remain unchanged along the length of the polypeptide and yield results consistent with short helix-forming peptides. From direct estimates of the density of states for Ac-ALA_n-NMe and the C-peptide homologues, the conformational entropy is calculated versus temperature. The calculated S(T) shows a clear proportionality to the chain length over a wide range of temperature. These results provide evidence for the validity of Flory's isolated pair hypothesis for non- local steric effects, at least in the context of helical peptides and helix-to-coil transitions in these peptides. We would also mention a new method of computing the conformational entropy (energy decomposition) which we have developed recently.

Reference: Y. Zenmei Ohkubo and Charles L. Brooks III, " Exploring Flory's isolated-pair hypothesis: Statistical mechanics of helix-coil transitions in polyalanine and the C-peptide from RNase A". Proc Natl Acad Sci U S A. 2003, 100(24):13916-21

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