On the relationship of thermodynamic parameters with the buried surface area in protein-ligand complex formation

1996 ◽  
Vol 16 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Netai C. Singha ◽  
Namita Surolia ◽  
A. Surolia
Keyword(s):  
Heat Capacity ◽  
High Resolution ◽  
Complex Formation ◽  
Thermodynamic Parameters ◽  
Hydrophobic Interactions ◽  
Structural Parameters ◽  
Structural Data ◽  
Rational Drug Design ◽  
Poor Correlation ◽  
Ligand Complex

Prediction of thermodynamic parameters of protein-protein and antigen-antibody complex formation from high resolution structural parameters has recently received much attention, since an understanding of the contributions of different fundamental processes like hydrophobic interactions, hydrogen bonding, salt bridge formation, solvent reorganization etc. to the overall thermodynamic parameters and their relations with the structural parameters would lead to rational drug design. Using the results of the dissolution of hydrocarbons and other model compounds the changes in heat capacity (ΔCp), enthalpy (ΔH) and entropy (ΔS) have been empirically correlated with the polar and apolar surface areas buried during the process of protein folding/unfolding and protein-ligand complex formation. In this regard, the polar and apolar surfaces removed from the solvent in a protein-ligand complex have been calculated from the experimentally observed values of changes in heat capacity (ΔCp) and enthalpy (ΔH) for protein-ligand complexes for which accurate thermodynamic and high resolution structural data are available, and the results have been compared with the x-ray crystallographic observations. Analyses of the available results show poor correlation between the thermodynamic and structural parameters. Probable reasons for this discrepancy are mostly related with the reorganization of water accompanying the reaction which is indeed proven by the analyses of the energetics of the binding of the wheat germ agglutinin to oligosaccharides.

scholarly journals Mechanistic insights into the interactions of dynein regulator Ndel1 with neuronal ankyrins and implications in polarity maintenance

2019 ◽  
Vol 117 (2) ◽  
pp. 1207-1215 ◽  
Author(s):  
Jin Ye ◽  
Jianchao Li ◽  
Fei Ye ◽  
Yan Zhang ◽  
Mingjie Zhang ◽  
...  
Keyword(s):  
Complex Formation ◽  
Hydrophobic Interactions ◽  
Coiled Coil ◽  
Structural Data ◽  
Giant Neuron ◽  
Ankyrin G ◽  
Regulator Protein ◽  
Coiled Coil Region ◽  
Mechanistic Basis ◽  
Cargo Sorting

Ankyrin-G (AnkG), a highly enriched scaffold protein in the axon initial segment (AIS) of neurons, functions to maintain axonal polarity and the integrity of the AIS. At the AIS, AnkG regulates selective intracellular cargo trafficking between soma and axons via interaction with the dynein regulator protein Ndel1, but the molecular mechanism underlying this binding remains elusive. Here we report that Ndel1’s C-terminal coiled-coil region (CT-CC) binds to giant neuron-specific insertion regions present in both AnkG and AnkB with 2:1 stoichiometry. The high-resolution crystal structure of AnkB in complex with Ndel1 CT-CC revealed the detailed molecular basis governing the AnkB/Ndel1 complex formation. Mechanistically, AnkB binds with Ndel1 by forming a stable 5-helix bundle dominated by hydrophobic interactions spread across 6 distinct interaction layers. Moreover, we found that AnkG is essential for Ndel1 accumulation at the AIS. Finally, we found that cargo sorting at the AIS can be disrupted by blocking the AnkG/Ndel1 complex formation using a peptide designed based on our structural data. Collectively, the atomic structure of the AnkB/Ndel1 complex together with studies of cargo sorting through the AIS establish the mechanistic basis for AnkG/Ndel1 complex formation and for the maintenance of axonal polarity. Our study will also be valuable for future studies of the interaction between AnkB and Ndel1 perhaps at distal axonal cargo transport.

Capability of the CANAPI algorithm to derive shrub structural parameters from satellite imagery in the Alaskan Arctic

Polar Record ◽  
2015 ◽  
Vol 52 (2) ◽  
pp. 124-133 ◽  
Author(s):  
Rocio R. Duchesne ◽  
Mark J. Chopping ◽  
Ken D. Tape
Keyword(s):  
High Resolution ◽  
Structural Parameters ◽  
Image Interpretation ◽  
Field Measurements ◽  
Structural Data ◽  
The Arctic ◽  
Regression Equations ◽  
Fractional Cover ◽  
High Resolution Imagery ◽  
Tundra Ecosystem

ABSTRACTThe observed greening of Arctic vegetation and the expansion of shrubs in the last few decades probably have profound implications for the tundra ecosystem, including feedbacks to climate. Uncertainty surrounding this vegetation shift and its implications calls for monitoring of vegetation structural parameters, such as fractional cover of shrubs. In this study, CANAPI, a semi-automated image interpretation algorithm that identifies and traces crowns by locating its crescent-shaped sunlit portion, was evaluated for its ability to derive structural data for tall (> 0.5 m) shrubs in the Arctic. CANAPI estimates of shrub canopy parameters were obtained from high-resolution imagery at 26 sites (250 m x 250 m each) by adjusting the algorithm's parameters and filter settings for each site, such that the number of crowns delineated by CANAPI roughly matched those observed in the high-resolution imagery. The CANAPI estimates were then compared with field measurements to evaluate the algorithm's performance. CANAPI successfully retrieved fractional cover (R2= 0.83,P< 0.001), mean crown radius (R2= 0.81,P< 0.001), and total number of shrubs (R2= 0.54,P< 0.001). CANAPI performed best in sparse vegetation where shrub canopies were distinct, while it tended to underestimate shrub cover where shrubs were clustered. The CANAPI algorithm and the regression equations presented here can be used in Arctic tundra environments to derive vegetation parameters from any sub-meter panchromatic imagery.

Tubulin structure at intermediate resolution

1995 ◽  
Vol 53 ◽  
pp. 852-853
Author(s):  
K. H. Downing ◽  
S. G. Wolf ◽  
E. Nogales
Keyword(s):  
High Resolution ◽  
Structural Data ◽  
Therapeutic Drug ◽  
Zinc Ions ◽  
Two Dimensional ◽  
X Ray Diffraction ◽  
X Ray ◽  
Negative Stain ◽  
Functional Mechanisms ◽  
Tubulin Structure

Microtubules are involved in a host of critical cell activities, many of which involve transport of organelles through the cell. Different sets of microtubules appear to form during the cell cycle for different functions. Knowledge of the structure of tubulin will be necessary in order to understand the various functional mechanisms of microtubule assemble, disassembly, and interaction with other molecules, but tubulin has so far resisted crystallization for x-ray diffraction studies. Fortuitously, in the presence of zinc ions, tubulin also forms two-dimensional, crystalline sheets that are ideally suited for study by electron microscopy. We have refined procedures for forming the sheets and preparing them for EM, and have been able to obtain high-resolution structural data that sheds light on the formation and stabilization of microtubules, and even the interaction with a therapeutic drug.Tubulin sheets had been extensively studied in negative stain, demonstrating that the same protofilament structure was formed in the sheets and microtubules. For high resolution studies, we have found that the sheets embedded in either glucose or tannin diffract to around 3 Å.

HRTEM study of valleriite, a hydroxide-bearing copper sulfide

1990 ◽  
Vol 48 (4) ◽  
pp. 462-463
Author(s):  
S. Wang ◽  
P. R. Buseck
Keyword(s):  
Electron Microscope ◽  
High Resolution ◽  
Copper Sulfide ◽  
Carbonaceous Chondrite ◽  
Structural Data ◽  
Basic Structure ◽  
Long Period ◽  
Selected Area Electron Diffraction ◽  
Transmission Electron ◽  
Wavy Structure

Valleriite is an unusual mineral, consisting of intergrowths of sulfide layers (corresponding in structure to the mineral smythite - Fe9S11) and hydroxide layers (corresponding to brucite - Mg(OH2)). It has a composition of approximately 1.526[Mg.68Al.32(OH)2].[Fe1.07Cu.93S2] and consists of two interpenetrating lattices, each of which retains its individual structural and diffraction characteristics parallel to the layering. The valleriite structure is related to that of tochilinite, an unusual iron-rich mineral that is of considerable interest for the origin of certain carbonaceous chondrite meteorites and to those of franckeite and cylindrite, two minerals that are of interest because of their unique morphological and crystallographic properties, e.g., the distinctive curved form of cylindrite and the perfect mica-like cleavage with unusual striations and the long-period wavy structure of franckeite.Our selected-area electron diffraction (SAED) patterns and high-resolution transmission electron microscope (HRTEM) images of valleriite provide new structural data. A basic structure and a new superstructure have been observed.

scholarly journals Thermodynamic and detailed kinetic study of the formation of orthophthalaldehyde-agmatine complex by fluorescence intensities

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Khémesse Kital ◽  
Moumouny Traoré ◽  
Diégane Sarr ◽  
Moussa Mbaye ◽  
Mame Diabou Gaye Seye ◽  
...  
Keyword(s):  
Complex Formation ◽  
Thermodynamic Parameters ◽  
Initial Rate ◽  
Reaction Medium ◽  
Standard Entropy ◽  
Step Size ◽  
Formation Reaction ◽  
Different Temperatures ◽  
Kinetics Of ◽  
Complex Formation Process

Abstract The aim of this work is to determine the thermodynamic parameters and the kinetics of complex formation between orthophthalaldehyde (OPA) and agmatine (AGM) in an alkaline medium (pH 13). Firstly, the association constant (Ka) between orthophthalaldehyde and agmatine was determined at different temperatures (between 298 K and 338 K) with a step size of 10 K. Secondly, the thermodynamic parameters such as standard enthalpy (ΔH°), standard entropy (ΔS°),and Gibbs energy (∆G) were calculated, where a positive value of ΔH° (+45.50 kJ/mol) was found, which shows that the reaction is endothermic. In addition, the low value of ΔS°(+0.24 kJ/mol) indicates a slight increase in the disorder in the reaction medium. Furthermore, the negative values of ΔG between −35.62 kJ/mol and −26.02 kJ/mol show that the complex formation process is spontaneous. Finally, the parameters of the kinetics of the reaction between OPA and AGM were determined as follows: when the initial concentration of AGM (5 × 10−6 M) is equal to that of the OPA, the results show that the reaction follows an overall 1.5 order kinetics with an initial rate of 5.1 × 10−7Mmin−1 and a half-life of 8.12 min. The partial order found in relation to the AGM is 0.8. This work shows that the excess of OPA accelerates the formation reaction of the complex.

scholarly journals Studies of Conformational Changes of Tubulin Induced by Interaction with Kinesin Using Atomistic Molecular Dynamics Simulations

2021 ◽  
Vol 22 (13) ◽  
pp. 6709
Author(s):  
Xiao-Xuan Shi ◽  
Peng-Ye Wang ◽  
Hong Chen ◽  
Ping Xie
Keyword(s):  
Molecular Dynamics ◽  
High Resolution ◽  
Binding Energy ◽  
Molecular Dynamics Simulations ◽  
Conformational Changes ◽  
Weak Interactions ◽  
Molecular Motor ◽  
Structural Data ◽  
Calculated Binding Energy ◽  
Dynamics Simulations

The transition between strong and weak interactions of the kinesin head with the microtubule, which is regulated by the change of the nucleotide state of the head, is indispensable for the processive motion of the kinesin molecular motor on the microtubule. Here, using all-atom molecular dynamics simulations, the interactions between the kinesin head and tubulin are studied on the basis of the available high-resolution structural data. We found that the strong interaction can induce rapid large conformational changes of the tubulin, whereas the weak interaction cannot. Furthermore, we found that the large conformational changes of the tubulin have a significant effect on the interaction of the tubulin with the head in the weak-microtubule-binding ADP state. The calculated binding energy of the ADP-bound head to the tubulin with the large conformational changes is only about half that of the tubulin without the conformational changes.

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