Calculation of nucleation free energy for duplex oligomers in the context of nearest neighbor models

Additive physical properties of DNA double strand polymers have been expanded in terms of 8 irreducible parameters. This provided consistency relations among the corresponding 10 duplex dimer contributions. To allow for oligomer analysis, end parameters were often added, and this would add extra degrees of freedom to the fore mentioned parameters. Statistical mechanics approaches were then connected to the nearest neighbor (NN) approach in the framework of the two‐states model. Ad hoc end effects were thus (wrongly) correlated to nucleation phenomena and this lead to a critique for its role in NN modeling. With this motivation, a new NN model is proposed that accommodates the nucleation free energies. The model relates the nucleation free energy to the mean composition of the chain and permits to obtain a good estimate for the free energy associated only to the Watson–Crick base pairings. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 538–547, 2013.     

Gibbs free energy in periodic enterobacterial cultures]

The authors present the results of study of the Gibbs' free energy (--delta G) output in periodic cultures of nonpathogenic and enteropathogenic escherichia, shigellae, salmonellae, Proteus, serratia, and klebsiellae in the hydrolysate broth in a special twelve--chamber cultivator. Graphic expression--deltaG = f(N) permitted to reveal differences in the energy characteristics of individual enterobacteria genera and species. It is supposed that such studies could be useful in the choice of redox-indicators during the construction of differential-diagnostic media for the laboratory diagnosis of intestinal infections.     

Some problems in the usage of Gibbs free energy in biochemistry

The usage of Gibbs free energy (G) in biochemistry is examined critically. The textbook formulation of the Second Law of Thermodynamics as applied to chemically-reacting systems is reviewed. Cognizance of the established theory and terminology of chemical thermodynamics leads to the conclusion that the symbol "delta G", as used in most biochemical calculations of free-energy change (e.g. in freeze-clamp study of steady-state metabolic processes), is erroneous. The instantaneous change, symbolized by the expression (delta G/delta xi) (with xi the degree of advancement of the reaction), is seen to be the correct form for describing the thermodynamic quality of the reactions of cell metabolism. Mathematical and graphical analysis of a sample reaction demonstrates the fundamental difference between delta G and (delta G/delta xi). Some problems in the application and interpretation of free-energy change in biochemical systems are reviewed: (1) Advances in protein dynamics have revealed the free-energy linkage properties of the enzyme molecule in binding/catalytic events of catalysis, demanding that we view the thermodynamics of elementary enzyme reactions with a finer eye. (2) The reality of metabolic microenvironments in vivo leads to equivocation in the significance of free-energy changes measured under macroscopic conditions in vitro. (3) The physicochemical character of reaction dynamics in the living cell may in some cases exceed the domain of validity of such thermodynamic state functions as Gibbs free energy.     

Mean free energy topology for nucleotide sequences of varying composition based on secondary structure calculations.

The mean free energy generated from the secondary structure of RNA sequences of varying length and composition has been studied by way of probability theory. The expected boundaries or maximal and minimal values of a given distribution are explored and a method for estimating error as a function of the number of shuffled sequences is also examined. For typical nucleotide sequences found in biologically active organisms, the mean free energy, free energy distributions and errors appear to be scalable in terms of a fixed set of algorithm-dependent parameters and the nucleotide composition of the particular sequence under evaluation. In addition, a general semi-analytical formula for predicting the mean free energy is proposed which, at least to first-order approximation, can be used to rapidly predict the mean free energy of any sequence length and composition of RNA. The general methodology appears to be algorithm independent. The results are expected to provide a reference point for certain types of analysis related to structure of RNA or DNA sequences and to assist in measuring the somewhat related matter of complexity in algorithm development. Some related applications are discussed.     

Oligo replication advantage driven by GC content and Gibbs free energy

Large scale DNA oligo pools are emerging as a novel material in a variety of advanced applications. However, GC content and length cause significant bias in amplification of oligos. We systematically explored the amplification of one oligo pool comprising of over ten thousand distinct strands with moderate GC content in the range of 35–65%. Uniqual amplification of oligos result to the increased Gini index of the oligo distribution while a few oligos greatly increased their proportion after 60 cycles of PCR. However, the significantly enriched oligos all have relatively high GC content. Further thermodynamic analysis demonstrated that a high value of both GC content and Gibbs free energy could improve the replication of specific oligos during biased amplification. Therefore, this double-G (GC content and Gibbs free energy) driven replication advantage can be used as a guiding principle for the sequence design for a variety of applications, particularly for data storage.

     

Template-directed synthesis of oligonucleotides under eutectic conditions

Summary One of the most important sets of model prebiotic experiments consists of reactions that synthesize complementary oligonucleotides from preformed templates under nonenzymatic conditions. Most of these experiments are conducted at 4°C using 0.01–0.1 M concentrations of activated nucleotide monomer and template (monomer equivalent). In an attempt to extend the conditions under which this type of reaction can occur, we have concentrated the reactants by freezing at –18°C, which is close to the NaCl–H₂O eutectic at –21°C.The results from this set of experiments suggest that successful syntheses can occur with poly(C) concentrations as low at 5×10^–4 M and 2MeImpG concentrations at 10^–3 M. It was also anticipated that this mechanism might allow the previously unsuccessful poly(A)-directed synthesis of oligo(U)s to occur. However, no template effect was seen with the poly(A) and ImpU system. The failure of these conditions to allow template-directed synthesis of oligo(U)s supports the previously proposed idea that pyrimidines may not have been part of the earliest genetic material.Because of the low concentrations of monomer and template that would be expected from prebiotic syntheses, this lower temperature could be considered a more plausible geologic setting for template-directed synthesis than the standard reaction conditions.     

Minimalist representations and the importance of nearest neighbor effects in protein folding simulations

In order to investigate the level of representation required to simulate folding and predict structure, we test the ability of a variety of reduced representations to identify native states in decoy libraries and to recover the native structure given the advanced knowledge of the very broad native Ramachandran basin assignments. Simplifications include the removal of the entire side-chain or the retention of only the Cbeta atoms. Scoring functions are derived from an all-atom statistical potential that distinguishes between atoms and different residue types. Structures are obtained by minimizing the scoring function with a computationally rapid simulated annealing algorithm. Results are compared for simulations in which backbone conformations are sampled from a Protein Data Bank-based backbone rotamer library generated by either ignoring or including a dependence on the identity and conformation of the neighboring residues. Only when the Cbeta atoms and nearest neighbor effects are included do the lowest energy structures generally fall within 4 A of the native backbone root-mean square deviation (RMSD), despite the initial configuration being highly expanded with an average RMSD > or = 10 A. The side-chains are reinserted into the Cbeta models with minimal steric clash. Therefore, the detailed, all-atom information lost in descending to a Cbeta-level representation is recaptured to a large measure using backbone dihedral angle sampling that includes nearest neighbor effects and an appropriate scoring function.     

Detecting spatial aggregation from distance sampling: a probability distribution model of nearest neighbor distance

Spatial point pattern is an important tool for describing the spatial distribution of species in ecology. Negative binomial distribution (NBD) is widely used to model spatial aggregation. In this paper, we derive the probability distribution model of event-to-event nearest neighbor distance (distance from a focal individual to its n-th nearest individual). Compared with the probability distribution model of point-to-event nearest neighbor distance (distance from a randomly distributed sampling point to the n-th nearest individual), the new probability distribution model is more flexible. We propose that spatial aggregation can be detected by fitting this probability distribution model to event-to-event nearest neighbor distances. The performance is evaluated using both simulated and empirical spatial point patterns.     

The standard Gibbs free energy change of hydrolysis of alpha-D-ribose 1-phosphate

The standard Gibbs free energy change of hydrolysis of α-d-ribose 1-phosphate has been measured at pH 7.0, ionic strength 0.1 m, and 25 °C by combining the corresponding values of the two following reactions: adenosine + H₂O ág adenine + ribose (ΔG^0′ = ?2.3 ± 0.1 kcal/mol), catalyzed by adenosine nucleosidase, and ribose 1-phosphate + adenine ág adenosine + P_i (ΔG^0′ = ?3.1 ± 0.1 kcal/mol), catalyzed by adenosine phosphorylase. The standard Gibbs free energy changes were calculated for both reactions from the equilibrium constant. A value of -5.4 ± 0.15 kcal/mol, comparable to that of other hemiacetal phosphoric esters, was obtained for the hydrolysis of ribose 1-phosphate.     

Testing polyols' compatibility with Gibbs energy of stabilization of proteins under conditions in which they behave as compatible osmolytes

It is generally believed that compatible osmolytes stabilize proteins by shifting the denaturation equilibrium, native state <--> denatured state toward the left. We show here that if osmolytes are compatible with the functional activity of the protein at a given pH and temperature, they should not significantly perturb this denaturation equilibrium under the same experimental conditions. This conclusion was reached from the measurements of the activity parameters (K(m) and k(cat)) and guanidinium chloride-induced denaturations of lysozyme and ribonuclease-A in the presence of five polyols (sorbitol, glycerol, mannitol, xylitol and adonitol) at pH 7.0 and 25 degrees C.     

Properties of the nearest neighbor interchange metric for trees of small size

The crossover or nearest neighbor interchange metric has been proposed for use in numerical taxonomy to obtain a quantitative measure of distance between classifications that are modeled as unrooted binary trees with labeled leaves. This metric seems difficult to compute and its properties are poorly understood. A variant called the closest partition distance measure has also been proposed, but no efficient algorithm for its computation has yet appeared and its relationship to the nearest neighbor interchange metric is incompletely understood. I investigate four conjectures concerning the nearest neighbor interchange and closest partition distance measures and establish their validity for trees with as many as seven labeled vertices. For trees in this size range the two distance measures are identical. If a certain decomposition property holds for the nearest neighbor interchange metric, then the two distance measures are also identical at small distances for trees of any size.     

A correction to the calculation of the Gibbs free energy of adsorption for biomolecules in ion-exchange systems

We wish to propose a correction to the methodology introduced by Gerstner et al. [J.A. Gerstner, J.A. Bell, S.M. Cramer, Biophys. Chem. 52 (1994) 97-106] for the calculation of Gibbs free energies of adsorption of biomolecules to ion-exchange systems. Our approach is based on the requirement that the mobile phase and stationary phase concentrations be expressed in exactly the same units and the equilibrium constant be strictly dimensionless. The Gibbs free energies of ion-exchange calculated based on this correction appear to be more negative than those originally calculated by Gertner et al.     

Temperatures of expired air under varying climatic conditions

Measurements of expiration temperatures were carried out under different climatic conditions. In one series of experiments the ambient air temperature was varied, in another the relative humidity of the ambient air. The temperatures of the ambient air ranged between –5°C and 30°C and the relative humidity between 10% and 90%. The results reveal a high variability of the expiration temperatures, when the ambient air temperature is changed, and almost constant expiration temperatures, when the relative humidity is altered but the ambient air temperature is kept constant. Nasal expiration temperatures are more sensitive to changes of the meteorological parameters than oral expiration temperatures.     

Identifying G-protein coupled receptors using weighted Levenshtein distance and the nearest neighbor method

G-protein coupled receptors （GPCRs） are a class of seven-helix transmembrane proteins that have been used in bioinformatics as the targets to facilitate drug discovery for human diseases. Although thousands of GPCR sequences have been collected, the ligand specificity of many GPCRs is still unknown and only one crystal structure of the rhodopsin-like family has been solved. Therefore, identifying GPCR types only from sequence data has become an important research issue. In this study, a novel technique for identifying GPCR types based on the weighted Levenshtein distance between two receptor sequences and the nearest neighbor method （NNM） is introduced, which can deal with receptor sequences with different lengths directly. In our experiments for classifying four classes （acetylcholine, adrenoceptor, dopamine, and serotonin） of the rhodopsin-like family of GPCRs, the error rates from the leave-one-out procedure and the leave-half-out procedure were 0.62% and 1.24%, respectively. These results are prior to those of the covariant discriminant algorithm, the support vector machine method, and the NNM with Euclidean distance.     

Terminal contributions for duplex oligonucleotide thermodynamic properties in the context of nearest neighbor models

Additive physical properties of DNA polymer duplexes have been expanded in terms of eight irreducible parameters that ultimately lead to consistency relations among the corresponding 10 duplex dimer contributions. End parameters are often added to allow for oligomer analysis which would add four extra degrees of freedom to the aforementioned parameters. Analysis of sufficient experimental data on oligomer duplexes allows for the unambiguous recovery of irreducible parameters. Values for free energy, enthalpy, and entropy are thus obtained, in terms of either irreducible or dimer decomposition sets. Here, a better adjust for the entropic (and enthalpic) irreducible parameters are obtained as we consider the more precise melting temperature data for the sequences of a given dataset. However, still large error estimates, and no clear distinction between the orientations of the terminal base pairs could yet be found. Finally, statistical mechanics approaches are applied for to connect the nearest neighbor approach to the two states model. Ad hoc end effects can be thus correlated to nucleation phenomena, leading to a critique for its role in nearest neighbor modeling.     

On the theory of indicator-dilution methods under varying blood-flow conditions

The theory of measurement of flow and volume by indicator dilution techniques is given in conditions of time-variable flow rates. It is shown that the usual Hamilton (1932,Am. J. Physiol.,99, 534–551) methods can be misleading if the flow changes at a rate of close to that of the transport function. Operated with support from the United States Army, Navy, and Air Force.