Structure and function of proteins and nucleic acid Progress report, 1 Jul. - 31 Dec. 1967

Conformation of pyridine nucleotide coenzymes by rotary dispersion and dichrois

A Fluorescent Probe at the Active Site of Alpha Chymotrypsin

Spectrofluorimetric analysis of mobility and polarity of active sites of alpha chymotrypsi

Assessing the impact of England's National Health Service R&D Health Technology Assessment program using the "payback" approach

Copyright © Cambridge University Press 2009Objectives: This study assesses the impact of the English National Health Service (NHS) Health Technology Assessment (HTA) program using the "payback" framework.Methods: A survey of lead investigators of all research projects funded by the HTA program 1993-2003 supplemented by more detailed case studies of sixteen projects.Results: Of 204 eligible projects, replies were received from 133 or 65 percent. The mean number of peer-reviewed publications per project was 2.9. Seventy-three percent of projects claimed to have had had an impact on policy and 42 percent on behavior. Technology Assessment Reports for the National Institute for Health and Clinical Excellence (NICE) had fewer than average publications but greater impact on policy. Half of all projects went on to secure further funding. The case studies confirmed the survey findings and indicated factors associated with impact.Conclusions: The HTA program performed relatively well in terms of "payback." Facilitating factors included the program's emphasis on topics that matter to the NHS, rigorous methods and the existence of "policy customers" such as NICE

Mean field approaches to the totally asymmetric exclusion process with quenched disorder and large particles

The process of protein synthesis in biological systems resembles a one dimensional driven lattice gas in which the particles (ribosomes) have spatial extent, covering more than one lattice site. Realistic, nonuniform gene sequences lead to quenched disorder in the particle hopping rates. We study the totally asymmetric exclusion process with large particles and quenched disorder via several mean field approaches and compare the mean field results with Monte Carlo simulations. Mean field equations obtained from the literature are found to be reasonably effective in describing this system. A numerical technique is developed for computing the particle current rapidly. The mean field approach is extended to include two-point correlations between adjacent sites. The two-point results are found to match Monte Carlo simulations more closely

Structurally specific thermal fluctuations identify functional sites for DNA transcription

We report results showing that thermally-induced openings of double stranded DNA coincide with the location of functionally relevant sites for transcription. Investigating both viral and bacterial DNA gene promoter segments, we found that the most probable opening occurs at the transcription start site. Minor openings appear to be related to other regulatory sites. Our results suggest that coherent thermal fluctuations play an important role in the initiation of transcription. Essential elements of the dynamics, in addition to sequence specificity, are nonlinearity and entropy, provided by local base-pair constraints

Multi-site H-bridge breathers in a DNA--shaped double strand

We investigate the formation process of nonlinear vibrational modes representing broad H-bridge multi--site breathers in a DNA--shaped double strand. Within a network model of the double helix we take individual motions of the bases within the base pair plane into account. The resulting H-bridge deformations may be asymmetric with respect to the helix axis. Furthermore the covalent bonds may be deformed distinctly in the two backbone strands. Unlike other authors that add different extra terms we limit the interaction to the hydrogen bonds within each base pair and the covalent bonds along each strand. In this way we intend to make apparent the effect of the characteristic helicoidal structure of DNA. We study the energy exchange processes related with the relaxation dynamics from a non-equilibrium conformation. It is demonstrated that the twist-opening relaxation dynamics of a radially distorted double helix attains an equilibrium regime characterized by a multi-site H-bridge breather.Comment: 27 pages and 10 figure

Highly Designable Protein Structures and Inter Monomer Interactions

By exact computer enumeration and combinatorial methods, we have calculated the designability of proteins in a simple lattice H-P model for the protein folding problem. We show that if the strength of the non-additive part of the interaction potential becomes larger than a critical value, the degree of designability of structures will depend on the parameters of potential. We also show that the existence of a unique ground state is highly sensitive to mutation in certain sites.Comment: 14 pages, Latex file, 3 latex and 6 eps figures are include

Imaging density disturbances in water with 41.3 attosecond time resolution

We show that the momentum flexibility of inelastic x-ray scattering may be exploited to invert its loss function, alowing real time imaging of density disturbances in a medium. We show the disturbance arising from a point source in liquid water, with a resolution of 41.3 attoseconds ($4.13 \times 10^{-17}$ sec) and 1.27 $\AA$ ($1.27 \times 10^{-8}$ cm). This result is used to determine the structure of the electron cloud around a photoexcited molecule in solution, as well as the wake generated in water by a 9 MeV gold ion. We draw an analogy with pump-probe techniques and suggest that energy-loss scattering may be applied more generally to the study of attosecond phenomena.Comment: 4 pages, 4 color figure

Thermodynamic and Kinetic Analysis of Sensitivity Amplification in Biological Signal Transduction

Based on a thermodynamic analysis of the kinetic model for the protein phosphorylation-dephosphorylation cycle, we study the ATP (or GTP) energy utilization of this ubiquitous biological signal transduction process. It is shown that the free energy from hydrolysis inside cells, $\Delta G$ (phosphorylation potential), controls the amplification and sensitivity of the switch-like cellular module; the response coefficient of the sensitivity amplification approaches the optimal 1 and the Hill coefficient increases with increasing $\Delta G$. We discover that zero-order ultrasensitivity is mathematically equivalent to allosteric cooperativity. Furthermore, we show that the high amplification in ultrasensitivity is mechanistically related to the proofreading kinetics for protein biosynthesis. Both utilize multiple kinetic cycles in time to gain temporal cooperativity, in contrast to allosteric cooperativity that utilizes multiple subunits in a protein.Comment: 19 pages, 7 figure