Biophysical questions

This chapter reviews some of the molecular biophysical questions that are raised by the properties of one class of channel-forming proteins, con-nexin, and that may be addressed through the study of connexin in reconstituted membrane systems. The first section introduces issues of biophysical interest and provides background information about connexin. The second section discusses the prospects for utilizing reconstituted systems to study the key questions, followed by a brief review of data from our laboratory. The final sections evaluate the findings and discuss future studies. 

Choose a relevant biological process and system. What are the biological/ biochemical/biophysical questions that are to be addressed This choice will of necessity involve only a small part of biological reality. We are in reductionist mode here the question of integration into a systems framework wUl, for the most part, be left to other publications. 

In this chapter we provide an introductory overview of the imphcit solvent models commonly used in biomolecular simulations. A number of questions concerning the formulation and development of imphcit solvent models are addressed. In Section II, we begin by providing a rigorous fonmilation of imphcit solvent from statistical mechanics. In addition, the fundamental concept of the potential of mean force (PMF) is introduced. In Section III, a decomposition of the PMF in terms of nonpolar and electrostatic contributions is elaborated. Owing to its importance in biophysics. Section IV is devoted entirely to classical continuum electrostatics. For the sake of completeness, other computational... 

Abstract To understand how membrane-active peptides (MAPs) function in vivo, it is essential to obtain structural information about them in their membrane-bound state. Most biophysical approaches rely on the use of bilayers prepared from synthetic phospholipids, i.e. artificial model membranes. A particularly successful structural method is solid-state NMR, which makes use of macroscopically oriented lipid bilayers to study selectively isotope-labelled peptides. Native biomembranes, however, have a far more complex lipid composition and a significant non-lipidic content (protein and carbohydrate). Model membranes, therefore, are not really adequate to address questions concerning for example the selectivity of these membranolytic peptides against prokaryotic vs eukaryotic cells, their varying activities against different bacterial strains, or other related biological issues. 

As just mentioned, there are a large number of unsolved problems in membrane biophysics, including the questions of local anisotropic diffusion, hysteresis, protein-lipid phase separations, the role of fluctuations in membrane fusion, and the mathematical problems of diffusion in two dimensions Stokes paradox). 

The decision on what type of screen to use in FBDD is affected by many different factors availability of protein for screening, compound selection, throughput, turnaround and rate of false positives and negatives. The resolution of these questions from target assessment directly impact the possibilities in this section. If there is not sufficient protein for a biophysical screen, a biochemical screen is the only choice. Protein that is not stable for... 

V. Adrian Parsegian is chief of the Laboratory of Physical and Structural Biology in the National Institute of Child Health and Human Development. He has served as Editor of the Biophysical Journal and President of the Biophysical Society. He is happiest when graduate students come up to him after a lecture and ask hard questions. 

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