How Accurate Must Potentials Be for Successful Modeling of Protein Folding?

Protein sequences are believed to have been selected to provide the stability of, and reliable renaturation to, an encoded unique spatial fold. In recently proposed theoretical schemes, this selection is modeled as ``minimal frustration,'' or ``optimal energy'' of the desirable target conformation over all possible sequences, such that the ``design'' of the sequence is governed by the interactions between monomers. With replica mean field theory, we examine the possibility to reconstruct the renaturation, or freezing transition, of the ``designed'' heteropolymer given the inevitable errors in the determination of interaction energies, that is, the difference between sets (matrices) of interactions governing chain design and conformations, respectively. We find that the possibility of folding to the designed conformation is controlled by the correlations of the elements of the design and renaturation interaction matrices; unlike random heteropolymers, the ground state of designed heteropolymers is sufficiently stable, such that even a substantial error in the interaction energy should still yield correct renaturation.Comment: 28 pages, 3 postscript figures; tared, compressed, uuencode

Freezing Transition of Random Heteropolymers Consisting of an Arbitrary Set of Monomers

Mean field replica theory is employed to analyze the freezing transition of random heteropolymers comprised of an arbitrary number ($q$) of types of monomers. Our formalism assumes that interactions are short range and heterogeneity comes only from pairwise interactions, which are defined by an arbitrary $q \times q$ matrix. We show that, in general, there exists a freezing transition from a random globule, in which the thermodynamic equilibrium is comprised of an essentially infinite number polymer conformations, to a frozen globule, in which equilibrium ensemble is dominated by one or very few conformations. We also examine some special cases of interaction matrices to analyze the relationship between the freezing transition and the nature of interactions involved.Comment: 30 pages, 1 postscript figur

Prevalence of malnutrition and intestinal parasites in preschool slum children in Lucknow

Objective: To assess the point prevalence of intestinal parasites and their association with nutritional parameters. Setting: Anganwadi centers under the Integrated Child Development Scheme (ICDS) in Lucknow, North India. Design: Cross-sectional survey. Methods: By random draw, 32 out of 153 Anganwadi centers were selected. All eligible subjects registered with the Anganwadi worker were enrolled. These were 1061 children (48.3% girls and 51.7% boys) between the ages of 1.5 to 3.5 years. Results: Of these, 67.6% were underweight (weight for age <- 2 SD), 62.8% were stunted (height for age <-2 SD) and 26.5% were wasted (weight for height <-2 SD). Parasites were detected in 17.5% (95% CI 15.3%-19.9%) children by a single direct fecal smear examination. Of these, Ascaris lumbricoides was found in 124 (68.1%) and Giardia lamblia in 60 (32.9%). There was no association between weight or height and parasite positivity. The mean hemoglobin levels for children who were smear positive versus smear negative for ascaris or giardia were 9.1 g/dl and 9.6 g/dl, respectively (p<0.0001). Conclusion: In the urban slums the point prevalence of intestinal parasites is 17.5% in the preschool children. Malnutrition and low hemoglobin levels are also widely prevalent. Urgent remedial steps are needed on community basis to improve their nutritional status and control parasitic infestation

Reductive Biotransformation of Ethyl Acetoacetate: A Comparative Studies using Free and Immobilized Whole Yeast Cells

Bioreduction of ethyl acetoacetate with free and immobilized yeast whole cell was achieved by using water and sucrose combination. After detachment from immobilized beads under basic condition, the corresponding ethyl(S)-(+)-3-hydroxybutanoate was isolated with 98 to 100% yield. Immobilized beads of yeast whole cell were prepared at different temperature which affects the morphology and physiology of the beads for the diffusion of the enzyme, which shown the maximum conversion of the substrate to products as compared to the free yeast whole cell

Is Heteropolymer Freezing Well Described by the Random Energy Model?

It is widely held that the Random Energy Model (REM) describes the freezing transition of a variety of types of heteropolymers. We demonstrate that the hallmark property of REM, statistical independence of the energies of states over disorder, is violated in different ways for models commonly employed in heteropolymer freezing studies. The implications for proteins are also discussed.Comment: 4 pages, 3 eps figures To appear in Physical Review Letters, May 199

Free Energy Self-Averaging in Protein-Sized Random Heteropolymers

Current theories of heteropolymers are inherently macrpscopic, but are applied to folding proteins which are only mesoscopic. In these theories, one computes the averaged free energy over sequences, always assuming that it is self-averaging -- a property well-established only if a system with quenched disorder is macroscopic. By enumerating the states and energies of compact 18, 27, and 36mers on a simplified lattice model with an ensemble of random sequences, we test the validity of the self-averaging approximation. We find that fluctuations in the free energy between sequences are weak, and that self-averaging is a valid approximation at the length scale of real proteins. These results validate certain sequence design methods which can exponentially speed up computational design and greatly simplify experimental realizations.Comment: 4 pages, 3 figure

Two State Behavior in a Solvable Model of β\beta-hairpin folding

Understanding the mechanism of protein secondary structure formation is an essential part of protein-folding puzzle. Here we describe a simple model for the formation of the $\beta$-hairpin, motivated by the fact that folding of a $\beta$-hairpin captures much of the basic physics of protein folding. We argue that the coupling of ``primary'' backbone stiffness and ``secondary'' contact formation (similar to the coupling between the ``secondary'' and ``tertiary'' structure in globular proteins), caused for example by side-chain packing regularities, is responsible for producing an all-or-none 2-state $\beta$-hairpin formation. We also develop a recursive relation to compute the phase diagram and single exponential folding/unfolding rate arising via a dominant transition state.Comment: Revised versio