Workshop on Chemical Spectroscopy, Protein Folding Dynamics and Polymer Dynamics

Argonne National Laboratory

10-11 October, 2000

 

Applications for the Backscattering Spectrometer on the

Long Wave Length Target Station (LWTS)

 

 

Organizers:

 

 

 

 

 

   Scope

  Proposal

  List of participants

  Secretaries

  Agenda

 

Scope

 

The workshop on Chemical Spectroscopy, Protein Folding Dynamics and Polymer Dynamics is part of an effort to develop the case for the 200 neV back-scattering instrument proposed for the Long Wavelength Target Station (LWTS) at the Spallation Neutron Source (SNS). It will take place at Argonne National Laboratory October 10-11 2000.

As in the other LWTS workshops the atmosphere is very informal and designed to promote free discussions, with invited lectures (maximum of 12), given not only by neutron scatters, of about 45 minutes including discussion. Following an introduction to the characteristics of the LWTS and two keynote talks, each lecture will present as much as possible new or unpublished results and most importantly introduces controversial issues of interest for the community. On the afternoon of the second day we will be break out into groups with interests centered on the science covered in the different sessions. Each group will produce 2-3 pages describing their ideas for research using inelastic/quasi-elastic neutron scattering and how it could be enabled by a LWTS at the SNS.

The workshop will be held at the Advanced Photon Source, which is located inside Argonne National Laboratory and walking distance from the Argonne Guest House.

Travel to and from Argonne can be arranged by invited participants. All travel expenses (airline ticket using US carriers, local transportation, accommodation and meals) will be reimbursed via the University of Tennessee. 

Proposal

 

The aim of this workshop is to highlight potential scientific achievements in the fields of chemistry and biology, which are likely to be attained with the use of neutron scattering at the Long Wavelength Target Station (LWTS) at the Spallation Neutron Source (SNS).

 

We may identify four research areas where inelastic (INS) and quasi-elastic neutron scattering (QENS) have made significant contributions in various fields of chemistry:

(1)               The study of molecular vibrations, where now INS is now truly complimentary to Raman and Infrared spectroscopy, and furthermore, benefits from the relative computational ease with which INS spectra can be related to intermolecular interactions.

(2)               The rotational ground state (tunnel-) splitting of small molecular groups (e.g. methyl) is extraordinarily sensitive to its surroundings. High resolution INS of such tunnel splittings has been successfully utilized in a wide variety of chemical problems, ranging from layering of methane films to the dynamics of polymers and biomolecules.

(3)               Both translational and rotational diffusive motions of molecules are accessible by quasi-elastic neutron scattering if the process is sufficiently fast compared with available instrumental resolution. Neutrons are unique in this application as both temporal (as in NMR) and spatial information on the motions can be obtained. Important applications of this technique are in the area of catalysis, i.e. molecular diffusion in catalytic materials.

(4)               The increasing importance of computational chemistry makes an ideal complement to INS and QENS, as, for example, molecular dynamics simulations are directly related to observables in INS experiments. This has become a central theme in modern applications of neutron scattering.

Since the LWTS is optimized for cold neutron flux we may expect that the current practical limit for the slowest observable time-scale of about 100 ns may be pushed somewhat lower, which would have a significant impact in areas of physical and inorganic chemistry.

Molecular biology, on the other hand, often requires systematic studies of a large range of similar molecules under slightly different conditions. For much of biology, it is the small differences between closely related systems, which are of importance. The large increase in flux on the LWTS will make such systematic studies possible for the first time, thereby enabling molecular biology and biotechnology to take a much fuller advantage of the power of the neutron scattering in the effort to provide detailed microscopic views of both structure and dynamics. Many experimental methods, including neutron scattering, will be required to understand cell function at the molecular level. This understanding is a vital precursor to our ability to control disease, improve biomaterials and preserve our natural environment for future generations.

Opportunities at the Long Wave Length Target Station

 

Dynamical properties of molecules are accessible by various experimental techniques including NMR, Raman scattering, infrared absorption and dielectric spectroscopy, as well as neutron scattering techniques. Such methods are often complementary and have several advantages over neutron scattering. NMR, for instance, covers a range of dynamical processes subject to stronger potentials, which therefore occur on longer timescales, and has a high sensitivity for impurities of low concentration. For the case of rotational or translational tunneling, for example, no method yields such a direct, model independent insight into the systems as INS. Moreover, neutrons interact weakly with atomic nuclei so that experimental results can be modeled on the basis of the first Born approximation and spectral intensities interpreted quantitatively. The application of neutron scattering methods to biological problems, on the other hand, has been severely limited by the inadequate flux of even the most powerful existing sources and lack of suitable instrumentation. Despite this serious limitation neutron scattering has played a significant role over the past 20 years in improving our understanding of the structure and dynamics, and hence the function, of biological macromolecules. The availability of a new, more intense source with appropriate instrumentation is vital if the promises of the past are to come to fruition in the coming decades.

 

Applications of the Inverse Geometry Spectrometer at LWTS:

 

 

 

 

Key areas where the LWTS will result in significant progress include the following.

 

         Quantum-mechanical tunneling

Spectroscopy of quantum mechanical tunneling by reorientation or translation of small molecules or protons, respectively, using neutrons had its origin as an exotic application of high-resolution neutron spectroscopy. However, neutron scattering, combined to NMR on complementary timescales has proven to be a very direct and powerful method for studying these phenomena, which are extraordinarily sensitive to details of the intermolecular interactions. The latter can now be modeled with high accuracy by computational studies, whereby in combination with tunneling spectroscopy much better intermolecular potentials can be extracted. While much of the potentials used in fundamental chemical studies are now obtained through ab-initio methods, phenomenological transferable pair potentials still play the most important role in computational studies involving very large systems, such as the exploration of reaction paths of real chemical manufacturing or in characterizing the interaction between two molecules in biological systems. Nonetheless, there are many examples of experiments on tunneling systems, which have not been successful because of very low beam intensities available at the highest resolution, which may be needed, for example, for molecular hydrogen ligands with a highly activated H-H bond. Tunnel splitting can be very small (0.1 (or less) to more than 100meV) and their actual magnitude varies rapidly with the height of the potential barrier. Much of the more recent work has revealed complex splitting of tunneling peaks and it is therefore increasingly important that very high resolution can be obtained. Tunneling is a fundamental process influencing dynamical properties of many different materials. For example, the low temperature properties of glasses are determined by two level tunneling states.

 

          Diffusional processes

 

 

         Polymer dynamics     

A recent workshop organized at Argonne National Laboratory on the “Structure, Dynamics, and Charge Transport in Polymeric Materials”, emphasized the importance and application of quasi-elastic and spin echo neutron spectroscopy. It was made clear that in order to investigate the interplay between charge transport by ions and motions of polymer chains the combination of NMR, neutron scattering and molecular dynamics simulations are crucial.

 

         The dynamics of macromolecular systems

One of the unique areas of research that will be developed at the proposed Long Wave Length Target Station (LWTS) is the dynamics of biological macromolecules. These show remarkably rich spectra on account of their complexity, which range from rapid local vibrations to very slow collective motions.

Although we can learn much about the functionality of biomolecules such as enzymes from knowledge of their structures, we need information on their motional properties if we are to fully understand their operation as molecular machines. As well as understanding the principles that lead from sequence to structure ('the protein folding problem'), we also need to understand those principles that lead from structure to dynamics and function. The wide range of time scales over which this information is needed requires the use of an arsenal of physical techniques, and neutron scattering with its wide dynamic range ought to be a central one.

As in other frontier areas of neutron scattering, the consequence of the limitations of the available sources has been that the few exploratory measurements of protein dynamics have been largely restricted to determining general characteristics. The next step would be to examine a more varied selection of proteins and other macromolecules in order to determine if diversity in internal motions accompanies the diversity of biological structures. Example includes studies of the dynamics of thermophilic or halophilic proteins, mutant proteins, partially folded proteins or proteins with substrates or inhibitors bound.

 

 

            The SNS (HPTS and LWTS) will enable such dynamical measurements as functions of, for example, solvent (concentration and type) and pressure, and will also expand the application of neutron scattering to a much wider range of systems. Appropriate partial deuteration will allow us to focus on the dynamics of different parts of the macromolecule such as active site or binding regions or the co-operative zippering or breathing motions of a protein segments at transition temperatures. Complementarily with other techniques will also be exploited more effectively. For example, X-ray diffuse scattering from protein crystals gives information on correlated displacements in and between protein molecules. Neutron scattering holds the promise of energy analysis of the coherent diffuse scattering, giving information on both the time and length scales of correlated motions between different unit cells and within proteins. Nanosecond time scale motion of macromolecule segments in solution will be accessible using the proposed Inverse Geometry Spectrometer, with an elastic resolution of 200 neV.

 

Concluding remarks:

 

            Chemical spectroscopy and molecular biology will continue to be a major growth area of active research in the coming decades and a battery of methods including neutron scattering will be required and thus open a huge field of research.

            The potential for new investigation of chemical and biomolecular vibration is greatest in the area of quasi-elastic (back scattering) and inelastic scattering using pulsed neutron sources. Pulsed sources and the time of flight technique offer inherent advantages, including potentially greater Q resolution, a larger dynamic range, access to the lowest energy transfers, and high energy resolution.

            A complete set of SNS spectrometers, including the proposed LWTS neV instrument, will give us access to the wide range of time scales involved. A particularly novel and attractive direction is the opening up of the slow time scale (~10^-7 s) regime through the use of very cold neutrons.

            As a result of this proposed workshop I expect that the participants from different areas will build on the ideas presented in this document, and accordingly produce a letter of intent for a new and revolutionary instrument for such studies at the LWTS.

 

HNB kindly thank Juergen Eckert and Kenneth Herwig for the helpful discussions and ideas on the preparation of this proposal.

Achievements of neutrons in biological science and technology

   Positions of all 21 proteins in the 30S sub-unit of the ribosome of E. coli, as well as the general arrangement of protein relative to RNA. Structural information has also been obtained on the HIV-1 reverse transcriptase sub-unit arrangement, and the spatial arrangement of E. coli RNA polymerase bound to DNA with and without transcription factors.

   Determination of function-critical hydrogen positions in enzymes, for example that in the catalytic triad of trypsin. Accessibility of labile hydrogen in different parts of lysozyme and other proteins. Orientations of ring systems and methyl rotors.

   Determination of solvent organization in proteins and other biomolecular systems at room and low temperatures. This work has rationalized, for the first time, the factors that apparently control water orientation at biomolecular interfaces.

   Determination of protein-DNA distribution in the nucleosome and of the RNA, protein, and lipid distribution in spherical viruses.

   Unique information has been obtained on solvent interactions in tRNA and halophilic proteins, and on detergent interactions with membrane proteins.

   Determination of water levels in different parts of starch granules, leading to a deeper understanding of the gelatinisation processes.

   Characterization of the large amplitude internal motions in small proteins, and of a dynamical transition that is correlated with function in bacteriorhodopsin.

   Determination of phospholipid multilayer structure by selective deuteration. Studies of motional processes in the bilayer have provided the basis for our present view of the bilayer as a dynamically rough and extremely soft surface.

   Characterization of adsorbed protein single and multilayers at the air/water and oil/water interface.

   Determination of the protein-detergent distribution in membrane protein crystals, and the localization of lipid in a lipoprotein.

   Structural information on the purple membrane, including hydration properties, localization of the retinal chromophore in bacteriorhodopsin, the positions of specific a -helices and the structure of trapped intermediates in the bacteriorhodopsin photocycle.

List of participants

 

 

 

Secretaries

           

                                                 

 

Comments contact: hbordallo@anl.gov