Molecular mobility of soluble collagen

Conformation structure of soluble collagen in anhydrous form, films and gels was studied by broad line NMR. An analysis of spectra points to partial ordering of polymer chains in the films and possible formation of secondary structure of collagen molecules by alpha-helix type. Distinction of gel spectra from those of films is explained by unordered rotation movements of the chain fragments at the expense of "superspiralization" of collagen molecules.     

Solitons and energy transfer along protein molecules

It is shown that the energy released in the hydrolysis of ATP molecules can be transferred in the form of vibration solitons along α-helical protein molecules. The vibration solitons are collective excitations travelling along a chain of successively arranged peptide groups and corresponding to amide I vibrations. The exceptional stability of solitons in one-dimensional structures can account for the small probability of their energy transforming into that of disordered heat motion.     

A new look on the formation and interaction of elementary particles in atoms and molecules including photoreaction centers

Possible role of high-energy bosons (virtual photons) is discussed with respect to the formation of elementary particles and their interaction in nucleus, many-electron atom, and molecule including photoreaction centers. Using properties of the photons, the expressions for calculations of the mass of particles, of the energy of electrons and their distances from nucleus in atoms, of the dissociation energy and distances between atoms in molecules were found which give results in good agreement with experimental data. This approach allows doing calculations in rather complicated system like photoreaction centers in which chlorophyll molecules form electron transfer chain.     

Solvent Dielectric Effect and Side Chain Mutation on the Structural Stability of Burkholderia cepacia Lipase Active Site: A Quantum Mechanical/Molecular Mechanics Study

Quantum mechanical and molecular dynamics methods were used to analyze the structure and stability of neutral and zwitterionic configurations of the extracted active site sequence from a Burkholderia cepacia lipase, histidyl-seryl-glutamin (His86-Ser87-Gln88) and its mutated form, histidyl-cysteyl-glutamin (His86-Cys87-Gln88) in vacuum and different solvents. The effects of solvent dielectric constant, explicit and implicit water molecules and side chain mutation on the structure and stability of this sequence in both neutral and zwitterionic forms are represented. The quantum mechanics computations represent that the relative stability of zwitterionic and neutral configurations depends on the solvent structure and its dielectric constant. Therefore, in vacuum and the considered non-polar solvents, the neutral form of the interested sequences is more stable than the zwitterionic form, while their zwitterionic form is more stable than the neutral form in the aqueous solution and the investigated polar solvents in most cases. However, on the potential energy surfaces calculated, there is a barrier to proton transfer from the positively charged ammonium group to the negatively charged carboxylat group or from the ammonium group to the adjacent carbonyl oxygen and or from side chain oxygen and sulfur to negatively charged carboxylat group. Molecular dynamics simulations (MD) were also performed by using periodic boundary conditions for the zwitterionic configuration of the hydrated molecules in a box of water molecules. The obtained results demonstrated that the presence of explicit water molecules provides the more compact structures of the studied molecules. These simulations also indicated that side chain mutation and replacement of sulfur with oxygen leads to reduction of molecular flexibility and packing.     

Determining the roles of different chain fragments in recognition of immunoglobulin fold

We examine sequence-to-structure specificity of beta-structural fragments of immunoglobulin domains. The structure specificity of separate chain fragments is estimated by computing the Z-score values in recognition of the native structure in gapless threading tests. To improve the accuracy of our calculations we use energy averaging over diverse homologs of immunoglobulin domains. We show that the interactions between residues of beta-structure are more determinant in recognition of the native structure than the interactions within the whole chain molecule. This result distinguishes immunoglobulins from more typical proteins where the interactions between residues of the whole chain normally recognize the native fold more accurately than interactions between the residues of the secondary structure residues alone [Reva,B. and Topiol,S. (2000) BIOCOMPUTING: Proceedings of the Pacific Symposium. World Scientific Publishing Co., pp. 168-178]. We also find that the predominant contributions of the secondary structure are produced by the four central beta-strands that form the core of the molecule. The results of this study allow us through quantitative means to understand the architecture of immunoglobulin molecules. Comparing the fold recognition data for different chain fragments one can say that beta-strands form a rigid frame for immunoglobulin molecules, whereas loops, with no structural role, can develop a broad variety of binding specificities. It is well known that protein function is determined by specific portions of a protein chain. This study suggests that the whole protein structure can be predominantly determined by a few fragments of chain which form the structural framework of the molecule. This idea may help in better understanding the mechanisms of protein evolution: strengthening a protein structure in the key framework-forming regions allows mutations and flexibility in other chain regions.     

Hydrogen-ion binding of polycytidylic acid immobilized between Langmuir layers of dimethyldioctadecylammonium (DODA) in thin multilayer films

The report describes the study of hydrogen-ion binding of Langmuir-Blodgett films contained with polycytidylic acid. A variety of multilayer films are analyzed and their UV absorption spectra are recorded. Poly (C) molecules established between dimethyldioctadecylammonium (DODA) layers are shown to exist in double stranded and semiprotonated form, independent of the pH value of the solution from which the films were made. A large hysteresis was found between forward and back proton titration of poly(C) immobilized in the LB films. This hysteresis points to a marked transference of both types of molecules during the film titration. This behavior also depends upon the types of molecules from which the films were made.     

Free‐energy function based on an all‐atom model for proteins

We have developed a free‐energy function based on an all‐atom model for proteins. It comprises two components, the hydration entropy (HE) and the total dehydration penalty (TDP). Upon a transition to a more compact structure, the number of accessible configurations arising from the translational displacement of water molecules in the system increases, leading to a water‐entropy gain. To fully account for this effect, the HE is calculated using a statistical‐mechanical theory applied to a molecular model for water. The TDP corresponds to the sum of the hydration energy and the protein intramolecular energy when a fully extended structure, which possesses the maximum number of hydrogen bonds with water molecules and no intramolecular hydrogen bonds, is chosen as the standard one. When a donor and an acceptor (e.g., N and O, respectively) are buried in the interior after the break of hydrogen bonds with water molecules, if they form an intramolecular hydrogen bond, no penalty is imposed. When a donor or an acceptor is buried with no intramolecular hydrogen bond formed, an energetic penalty is imposed. We examine all the donors and acceptors for backbone‐backbone, backbone‐side chain, and side chain‐side chain intramolecular hydrogen bonds and calculate the TDP. Our free‐energy function has been tested for three different decoy sets. It is better than any other physics‐based or knowledge‐based potential function in terms of the accuracy in discriminating the native fold from misfolded decoys and the achievement of high Z‐scores. Proteins 2009. © 2009 Wiley‐Liss, Inc.     

Computer simulation of water in cytochrome c oxidase

Statistical mechanics and molecular dynamics simulations have been carried out to study the distribution and dynamics of internal water molecules in bovine heart cytochrome c oxidase (CcO). CcO is found to be capable of holding plenty of water, which in subunit I alone amounts to about 165 molecules. The dynamic characterization of these water molecules is carried out. The nascent water molecules produced in the redox reaction at the heme a(3)-CuB binuclear site form an intriguing chain structure. The chain begins at the position of Glu242 at the end of the D channel, and has a fork structure, one branch of which leads to the binuclear center, and the other to the propionate d of heme a(3). The branch that leads to the binuclear center has dynamic access both to the site where the formation of water occurs, and to delta-nitrogen of His291. From the binuclear center, the chain continues to run into the K channel. The stability of this hydrogen bond network is examined dynamically. The catalytic site is located at the hydrophobic region, and the nascent water molecules are produced at the top of the energy hill. The energy gradient is utilized as the mechanism of water removal from the protein. The water exit channels are explored using high-temperature dynamics simulations. Two putative channels for water exit from the catalytic site have been identified. One is leading directly toward Mg(2+) site. However, this channel is only open when His291 is dissociated from CuB. If His291 is bound to CuB, the only channel for water exit is the one that originates at E242 and leads toward the middle of the membrane. This is the same channel that is presumably used for oxygen supply.     

Regulation of intracellular trafficking of human CD1d by association with MHC class II molecules

CD1 family members are antigen-presenting molecules capable of presenting bacterial or synthetic glycolipids to T cells. Here we show that a subset of human CD1d molecules are associated with major histocompatibility complex (MHC) class II molecules, both on the cell surface and in the late endosomal/lysosomal compartments where class II molecules transiently accumulate during transport. The interaction is initiated in the endoplasmic reticulum with class II-invariant chain complexes and appears to be maintained throughout the class II trafficking pathway. A truncated form of CD1d which lacks its cytoplasmic YXXZ internalization motif is transported to late endosomal/lysosomal compartments in the presence of class II molecules. Furthermore, the same CD1d deletion mutant is targeted to lysosomal compartments in HeLa cells expressing class II molecules and invariant chain by transfection. The deletion mutant was also found in lysosomal compartments in HeLa cells expressing only the p33 form of the invariant chain. These data suggest that the intracellular trafficking pathway of CD1d may be altered by class II molecules and invariant chain induced during inflammation.     

The gramicidin A channel: energetics and structural characteristics of the progression of a sodium ion in the presence of water

The distribution of water molecules in the Gramicidin A (GA) channel is determined by theoretical computations, and the role of this water on the energetics of the system upon progression of a sodium cation through the channel is investigated. In the absence of the ion, water molecules form a chain along the channel, hydrogen bonded to one another and to the L carbonyl oxygens, while others stay at the entrances of the channel, hydrogen-bonded to the free carbonyl oxygens of the L-Tryptophan residues. According to the definition adopted for the "inside" and the "outside" of the channel, it is found to contain at most 7 or 9 water molecules. When a hydrated sodium cation approaches and enters the channel, the structural properties corresponding to the minimized total energy of the system GA-water-Na+ indicate a reorganization, but not a destruction, of the chain of water molecules. The "energy profile" for the system GA-Na+-(22 waters) is analyzed in terms of its components and in comparison to the corresponding intrinsic profile computed earlier in vacuo. It appears that the presence of water does not unduely modify the pathway or the qualitative features of the energetics of the cation passage, except at the entrance, where the partial and progressive dehydration of the cation plays an important role. The presence and characteristics of the minimum found earlier at 10.5 A from the center are conserved.     

Specificity of the initial collapse in the folding of the cold shock protein

The two-state folding reaction of the cold shock protein from Bacillus caldolyticus (Bc-Csp) is preceded by a rapid chain collapse. A fast shortening of intra-protein distances was revealed by F?rster resonance energy transfer (FRET) measurements with protein variants that carried individual pairs of donor and acceptor chromophores at various positions along the polypeptide chain. Here we investigated the specificity of this rapid compaction. Energy transfer experiments that probed the stretching of strand beta2 and the close approach between the strands beta1 and beta2 revealed that the beta1-beta2 hairpin is barely formed in the collapsed form, although it is native-like in the folding transition state of Bc-Csp. The time course of the collapse could not be resolved by pressure or temperature jump experiments, indicating that the collapsed and extended forms are not separated by an energy barrier. The co-solute (NH4)2SO4 stabilizes both native Bc-Csp and the collapsed form, which suggests that the large hydrated SO4(2-) ions are excluded from the surface of the collapsed form in a similar fashion as they are excluded from folded Bc-Csp. Ethylene glycol increases the stability of proteins because it is excluded preferentially from the backbone, which is accessible in the unfolded state. The collapsed form of Bc-Csp resembles the unfolded form in its interaction with ethylene glycol, suggesting that in the collapsed form the backbone is still accessible to water and small molecules. Our results thus rule out that the collapsed form is a folding intermediate with native-like chain topology. It is better described as a mixture of compact conformations that belong to the unfolded state ensemble. However, some of its structural elements are reminiscent of the native protein.     

Solid‐State Solar Thermal Fuels for Heat Release Applications

Closed cycle systems offer an opportunity for solar energy harvesting and storage all within the same material. Photon energy is stored within the chemical conformations of molecules and is retrieved by a triggered release in the form of heat. Until now, such solar thermal fuels (STFs) have been largely unavailable in the solid‐state, which would enable them to be utilized for a multitude of applications. A polymer STF storage platform is synthesized employing STFs in the solid‐state. This approach enables uniform films capable of appreciable heat storage of up to 30 Wh kg^?1 and that can withstand temperature of up to 180 °C. For the first time a macroscopic energy release is demonstrated using spatial infrared heat maps with up to a 10 °C temperature change. These findings pave the way for developing highly efficient and high energy density STFs for applications in the solid‐state.     

Imaging of kinked configurations of DNA molecules undergoing orthogonal field alternating gel electrophoresis by fluorescence microscopy

The dynamics of individual DNA molecules undergoing orthogonal field alternating gel electrophoresis (OFAGE) have been studied by use of T2 DNA molecules labeled with a dye and visualized with a fluorescence microscope. The mechanism of reorientation used by a molecule to align itself in the direction of the new orthogonal field depends on the degree of extension of the chain immediately before the application of this field. The formation of kinks is promoted when time is allowed between the application of the two orthogonal fields so that the molecule attains a partially relaxed configuration. In this case, the chain appears bunched up in domains moving along the contour of the molecule. These regions are found to be the locations where the kinks are formed upon application of the second field perpendicular to the chain. The formation of kinks provides a significant retardation of the reorientation of the molecules, relative to molecules that do not form kinks, and appears to play an important role in the fractionation attained with OFAGE. A classification of various reorientation mechanisms observed in molecules that form kinks is presented.     

Some remarks on molecular biology

The binding energy of a very long molecular chain, composed of different classes of molecules, depends in general on the order of the molecules. It is shown that under very general conditions there exists for a givenbrutto chemical composition of a chain, a class of chains which is characterized by a total binding energy which is equal to the total binding energy of any other prescribed chain of different composition within the limits of unsharpness of the energy level. This establishes a criterion formapping of a class of configurations of long chain molecules on another class. To the extent that a mapping constitutes a generalized code those results contribute to the theory of molecular codes. Applying to our results the results of a previous paper (1959,Bull. Math. Biophysics,21, 309–326), we arrive at the conclusion that the self-replication of a living molecule may be the property not of a particular structure but of classes of structures.     

Conformational analysis of some phenethylamine molecules

A set of empirical potential functions (EPF), previously used in conformational energy calculations of polymers, was employed in the study of the conformational properties of a number of methyl-substituted phenethylmines, as well as phenylmethylamine, phenyl-n-propylamine, and 3,4,5-trimethoxyamphetamine. The conformational free energy was computed for each of these molecular species in four states: neutral charge-vacuo (I), neutral charge-aqueous solution (II), positive charge-vacuo (III), positive charge-aqueous solution (IV). The molecules generally adopt one of two stable conformations: a folded conformation with the amine chain perpendicular to the ring, and the amine group nearest to the ring; and an extended conformation with the amine chain perpendicular to the ring, and the amine group far from the ring. The folded conformation is usually preferred for states I, II and III, while the extended form is adopted for state IV. By using empirical potential functions it was also possible to calculate the conformational entropies associated with the minimum energy conformations, thereby allowing the Boltzmann probabilities to be determined. These probabilities are a measure of the population density of each of the various low energy regions. Some of the molecules studied have a steric “bulge” below the plane of the benzene ring. All of the compounds studied which possess this “bulge” are psychotropically inactive, and, in most cases, also pharmacologically inactive. All active compounds studied do not possess this “bulge”.     

Release of phospholipids from colloidal particles to polymeric surfaces

This study presents a small-scale polymerization of high molecular weight methyl methacrylate/n-butyl acrylate (MMA/n-BA) colloidal particles that are synthesized in an aqueous environment in the presence of phospholipid hydrogenated soybean phosphatidylcholine (HSPC) molecules that also serve as the particle stabilizing agents. When such particles coalesce to form polymeric films, they release phospholipids, which, in turn, form organized structures near the film-air (F-A) interface. Diffusion and mobility of phospholipid molecules are affected not only by their compatibility with colloidal particles but also by electrolyte environments of colloidal dispersions. When Na(+), K(+), and Ca(2+) counterions are added to MMA/n-BA aqueous colloidal dispersions stabilized with HSPC, and such films are coalesced, different degrees of diffusion of HSPC to the F-A interface exist, depending on the counterion, and conformational changes of HSPC result. For example, in the presence of Ca(2+), HSPC molecules collapse entropically to form random surface layers, as opposed to smaller Na(+) and K(+), which force amphiphilic HSPC ends to align preferentially parallel to the film surface. These studies show that it is possible to design stimuli-response colloidal systems triggered by chemical environments of active molecules on colloidal polymer particles.     

The effect of low intensity electromagnetic irradiation on hydration of DNA film

By using the IR-spectroscopy it has been shown that electromagnetic radiation (frequency 8.15-10.0 GHz, energy flux density 5 microWt/cm2) reduces the rate of water desorption from DNA films. It was found that the irradiation of samples with high humidity did not change spectral characteristics of DNA molecules in the range of 900-4000 cm-1, that means their molecular structure remains intact. At the same time the irradiation changed conformation liability of these biopolymeric molecules, that is their ability of conformational transformations under the influence of outer factors. Drying of non-irradiated humid films induced rapid (for a few minutes) transition of DNA from B to A conformational state, whereas in the irradiated films this transition took several hours after humidity reducing.     

Inhibitors can activate proteases to catalyze the synthesis and hydrolysis of peptides

Competitive inhibitors can activate proteases (papain, trypsin, and cathepsin S) to catalyze the synthesis of peptide bonds and accelerate the hydrolysis of poor substrates (from 1 to 99%). Reaction mixtures contained intermediate molecules that were formed by the coupling of the inhibitor with the poor substrate. This and other findings suggest the following chain of events. Part of the binding energy of formation of the enzyme-inhibitor complex was used to activate the inhibitor, i.e., to form acyl-enzyme species with a high-energy bond (e.g., a thioester bond in the case of papain) required for coupling the inhibitor with the substrate to form the intermediate molecule. The latter was subjected to successive reactions which led to a stepwise degradation of the substrate, as well as to the regeneration of the inhibitor. One mole of the inhibitor could catalyze rapid hydrolysis of at least 53 mol of substrate. The intermediate molecules were the species undergoing rapid hydrolysis. Therefore, 1 mol of inhibitor was involved in the synthesis of 53 mol of intermediate molecules; i.e., the inhibitor functioned as a cofactor that catalyzed the synthesis of peptides. Thus, the binding energy of formation of the enzyme-inhibitor complex can be utilized to catalyze the synthesis of peptide bonds in the absence of an exogenous energy source (e.g., ATP).     

Surface film pressure of actin: interactions with lipids in mixed monolayers

The interactions of actin with neutral lipid films made from DLPC, and with positively charged films built from DLPC and stearylamine (SA), have been characterized by the monolayer technique. Injection of actin underneath an expanded lipid film produces an increase in the surface pressure that is consistent with a penetration of the lipid molecules by actin. This adsorption of actin to the lipid is more pronounced either with positively charged films or with Mg(2+) present in the sub-phase, suggesting that the mechanism involves an electrostatic attraction. During compression, the actin molecules are squeezed out into the sub-phase, carrying along some lipid molecules; this suggests a strong affinity of the lipids for actin. An analysis of the dilational modulus shows that when actin is found as monomers at the interface, the mixed actin-lipid film undergoes three phase changes upon compression. On the other hand, when actin is polymerized at the interface, the actin and the lipid form a rigid film for which the compressibility is mostly dominated by actin.     

Electrostatic interactions in polyglutamic acid

Conformational energy estimates were made for completely charged polyglutamic acid with different assumptions concerning the placement of side chain charge. Viewed as a helix, the minimum energy structure is somewhat affected by the side-chain charge placement. The average energy of the chain viewed as a random coil is equal to or less than the average energy of the chain viewed as a helix. Unlike the polyacrylate chain, nearest-neighbor charge interaction is shown to increase the chain dimensions. Although the calculations are approximate there is little evidence to suggest that isolated polyglutamate molecules in the absence of added electrolyte should behave as rods or that there are significant amounts of locally ordered structures. Presently no experimental results exist under conditions appropriate to isolated molecular calculations.