From Spirolactam Mixtures to Regioisomerically Pure 5- and 6-Rhodamines: A Chemodosimeter-Inspired Strategy

Inspired by the ring-open reaction of rhodamine spriolactams as typical chemodosimeters, a general strategy is proposed to conveniently and efficiently synthesize isomerically pure 5- and 6-R-tetramethylrhodamine on a larger scale

Replacing Phenyl Ring with Thiophene: An Approach to Longer Wavelength Aza-dipyrromethene Boron Difluoride (Aza-BODIPY) Dyes

In the orignial 1,3,5,7-tetraphenyl aza-BODIPY, replacing the phenyl rings with thiophene achieved significant bathochromic shifts. One of the target molecules, <b>DPDTAB</b>, emitting strong NIR fluorescence with a quantum yield of 0.46 in acetonitrile, is a very competitive NIR fluorophore

Replacing Phenyl Ring with Thiophene: An Approach to Longer Wavelength Aza-dipyrromethene Boron Difluoride (Aza-BODIPY) Dyes

In the orignial 1,3,5,7-tetraphenyl aza-BODIPY, replacing the phenyl rings with thiophene achieved significant bathochromic shifts. One of the target molecules, <b>DPDTAB</b>, emitting strong NIR fluorescence with a quantum yield of 0.46 in acetonitrile, is a very competitive NIR fluorophore

A Lysosome-Targetable and Two-Photon Fluorescent Probe for Monitoring Endogenous and Exogenous Nitric Oxide in Living Cells

A lysosome-specific and two-photon fluorescent probe, <b>Lyso-NINO</b>, demonstrates high selectivity and sensitivity toward NO, lower cytotoxicity, and perfect lysosomal localization. With the aid of <b>Lyso-NINO</b>, the first capture of NO within lysosomes of macrophage cells has been achieved using both two-photon fluorescence microscopy and flow cytometry

Replacing Phenyl Ring with Thiophene: An Approach to Longer Wavelength Aza-dipyrromethene Boron Difluoride (Aza-BODIPY) Dyes

In the orignial 1,3,5,7-tetraphenyl aza-BODIPY, replacing the phenyl rings with thiophene achieved significant bathochromic shifts. One of the target molecules, <b>DPDTAB</b>, emitting strong NIR fluorescence with a quantum yield of 0.46 in acetonitrile, is a very competitive NIR fluorophore

Structural Properties of the Closed Myosin Active Site During Equilibrium MD Simulations with Different Nucleotide Chemical States (ATP or ADP·P<i>_i</i>)

<div><p>(A–D) Instantaneous distances between Mg²⁺ and oxygen atoms in its four nonwater ligands. (A) MM ATP state. (B) MM ADP·P<i>_i</i> state. (C) QM/MM ATP state. (D) QM/MM ADP·P<i>_i</i> state. O^1ß refers to O^1ß in ATP or ADP; O^1γ refers to O^1γ in ATP or the closest oxygen atom in P<i>_i</i>; O^Ser237 refers to O^γ in Ser237; O^Thr186 refers to O^γ2 in Thr186.</p><p>(E) Overlay of the active site in two snapshots from MM simulations with ATP and ADP·P<i>_i</i>, respectively. The one with color coding is for the ATP state while the one in grey is for the ADP·P<i>_i</i> state. The Mg²⁺-O^Ser237 distance is much longer in the ADP·P<i>_i</i>-state snapshot, due to displacements in both the Ser237 sidechain and the hydrolyzed nucleotide.</p><p>(F) Root mean square fluctuation (RMSF) for Cα atoms in the three critical active-site motifs based on equilibrium MM simulations. Ser237 has notably larger fluctuations in the ADP·P<i>_i</i> state, although the rest residues do not show distinct differences.</p></div

The Hinge Residues (Shown in the van der Waals Form) Identified by DynDom [84,85] Based on Results of Normal Mode Analysis

<div><p>See <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0030023#pcbi-0030023-t002" target="_blank">Table 2</a> and in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0030023#pcbi-0030023-sd001" target="_blank">Protocol S1</a> Tables B1–B4 and B6.</p><p>Upper 50-kD domain, lower 50-kD domain, converter domain, and central β sheet are shown in red, silver, purple, and cyan, respectively. Strut loop, relay helix, P-loop, Switch I and Switch II, and SH1 helix are shown in yellow. The rest of the protein is shown in green. The hinge residues are colored based on residue type—blue, basic; orange, acidic; slate blue, polar; white, nonpolar. The four figures are based on modes with large involvement coefficients for different transitions: (A) 1FMW → 1VOM, (B) 1VOM → 1Q5G, (C) 1Q5G → 1FMW, (D) 1VOM → 1FMW.</p></div

The Lymn–Taylor Functional Cycle of Myosin-II–Actin [13–17]

<p>Only a myosin monomer is shown for simplicity. The binding of ATP to the actin–myosin complex (the “rigor state”) leads to rapid dissociation of myosin from actin without immediate hydrolysis of ATP. Coupled with a major structural change in the orientation of the lever arm (recovery stroke), ATP hydrolysis proceeds, after which the motor domain rebinds to actin weakly. Following the release of P<i>_i,</i> the motor domain undergoes “powerstroke” during which the orientation of the lever arm changes back to that in the “rigor state” and the motor domain becomes strongly bound to actin. Dissociation of ADP leads the system back to the “rigor state.” Note that the sum of free-energy drops in an entire cycle is equal to the hydrolysis free energy of ATP in <i>solution,</i> which is the ultimate thermodynamic driving force of the system.</p

PMF Calculations for the Open/Close of the Active Site with Different Converter Orientations

<div><p>The reaction coordinate for 1-D PMFs is Δ<i>RMSD</i> relative to the open and closed active-site configurations; those for 2-D PMFs are <i>RMSD</i>s relative to the open and closed active-site configurations.</p><p>(A,B) PMFs (in kcal/mol) for the 1FMW:ATP state.</p><p>(C,D) PMFs (in kcal/mol) for the 1VOM:ATP state.</p><p>(E,F) PMFs (in kcal/mol) for the 1VOM:ADP·P<i>_i</i> state.</p><p>(G) Superimposition of the final structure from the 1FMW:ATP simulation at Δ<i>D_min</i> = 2.2 Å (opaque) and the closed reference structure (transparent).</p><p>(H) Superimposition of the final structure from the 1VOM:ATP simulation at Δ<i>D_min</i> = 2.2Å (opaque) and the open reference structure (transparent).</p></div

Structural Differences between Conformations of the D. discoideum Myosin Motor Domain

<div><p>(A) The difference between the post-rigor (1FMW [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0030021#pcbi-0030021-b018" target="_blank">18</a>]) and pre-powerstroke (1VOM [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.0030021#pcbi-0030021-b019" target="_blank">19</a>]) states. The structures are aligned based on backbone atoms in the first 650 residues; red and blue correspond to 1FMW, green and yellow correspond to 1VOM. Trp501 is shown in the van der Waals form.</p><p>(B) Superposition of the active-site region in 1FMW and 1VOM (same color coding as in (A); the nucleotide is shown in the van der Waals form).</p><p>(C) Superposition of the relay helix and relay loop in 1FMW and 1VOM with the same color coding as in (A).</p></div