PIP2-Binding Site in Kir Channels: Definition by Multiscale Biomolecular Simulations†

Phosphatidylinositol bisphosphate (PIP(2)) is an activator of mammalian inwardly rectifying potassium (Kir) channels. Multiscale simulations, via a sequential combination of coarse-grained and atomistic molecular dynamics, enabled exploration of the interactions of PIP(2) molecules within the inner leaflet of a lipid bilayer membrane with possible binding sites on Kir channels. Three Kir channel structures were investigated: X-ray structures of KirBac1.1 and of a Kir3.1-KirBac1.3 chimera and a homology model of Kir6.2. Coarse-grained simulations of the Kir channels in PIP(2)-containing lipid bilayers identified the PIP(2)-binding site on each channel. These models of the PIP(2)-channel complexes were refined by conversion to an atomistic representation followed by molecular dynamics simulation in a lipid bilayer. All three channels were revealed to contain a conserved binding site at the N-terminal end of the slide (M0) helix, at the interface between adjacent subunits of the channel. This binding site agrees with mutagenesis data and is in the proximity of the site occupied by a detergent molecule in the Kir chimera channel crystal. Polar contacts in the coarse-grained simulations corresponded to long-lived electrostatic and H-bonding interactions between the channel and PIP(2) in the atomistic simulations, enabling identification of key side chains

Molecular Biomechanics: The Molecular Basis of How Forces Regulate Cellular Function

Recent advances have led to the emergence of molecular biomechanics as an essential element of modern biology. These efforts focus on theoretical and experimental studies of the mechanics of proteins and nucleic acids, and the understanding of the molecular mechanisms of stress transmission, mechanosensing and mechanotransduction in living cells. In particular, single-molecule biomechanics studies of proteins and DNA, and mechanochemical coupling in biomolecular motors have demonstrated the critical importance of molecular mechanics as a new frontier in bioengineering and life sciences. To stimulate a more systematic study of the basic issues in molecular biomechanics, and attract a broader range of researchers to enter this emerging field, here we discuss its significance and relevance, describe the important issues to be addressed and the most critical questions to be answered, summarize both experimental and theoretical/computational challenges, and identify some short-term and long-term goals for the field. The needs to train young researchers in molecular biomechanics with a broader knowledge base, and to bridge and integrate molecular, subcellular and cellular level studies of biomechanics are articulated.National Institutes of Health (U.S.) (grant UO1HL80711-05 to GB)National Institutes of Health (U.S.) (grant R01GM076689-01)National Institutes of Health (U.S.) (grant R01AR033236-26)National Institutes of Health (U.S.) (grant R01GM087677-01A1)National Institutes of Health (U.S.) (grant R01AI44902)National Institutes of Health (U.S.) (grant R01AI38282)National Science Foundation (U.S.) (grant CMMI-0645054)National Science Foundation (U.S.) (grant CBET-0829205)National Science Foundation (U.S.) (grant CAREER-0955291

Thermal conductivity of high- T c superconductors

This paper reviews existing data on the thermal conductivity of high- T c superconductors. Included are discussions of pristine polycrystalline high- T c ceramics, single crystal specimens, and high- T c materials structurally modified by substitution or by radiation damage. The thermal conductivity of high- T c superconductors is compared with that of conventional superconductors, and dramatic differences are found between the two families. Mechanisms of thermal conductivity applicable to high- T c perovskites are discussed and implications for theories of high- T c superconductivity are noted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45121/1/10948_2004_Article_BF00617463.pd

Continuum Dislocation Dynamics: Classical Theory and Contemporary Models

The continuum theory of dislocation fields is discussed in this chapter with an emphasis on the formulations relevant to infinitesimal deformation of single crystals. Both the classical and contemporary developments are concisely outlined. The classical theory of dislocation fields is introduced first for static and dynamic dislocation configurations, followed by a brief discussion of the shortcomings of the classical theory in predicting plasticity of crystals. In this regard, the lack of connection between the evolution of the dislocation field and internal stress state of the crystal is particularly highlighted. The more recent phenomenological and statistically-based formalisms of continuum dislocation dynamics are then introduced. As discussed in the pertinent sections, these formalisms properly connect the evolution of the dislocation fields with the internal stress state in and thus offer frameworks for predicting the plastic behavior of crystals

ANDREW BAIN TRANSFORM: MULTIPLE CONTINENTAL-TYPE TRANSFORM BOUNDARIES AT MID-OCEAN RIDGE

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