Free energy calculations

This is a prospective submission to the Journal Scientific American or an affiliate, however I have decided to release it early for the interest of the public, since it is unlikely to be accepted. I still hope this paper is taken to be significant to science.

A typical Alternating Current (AC) transformer utilizes a principle of transferring electrical energy called mutual electromagnetic induction. This effect described as Faraday's Law of Induction (1831) permits a near equal amount of REAL power to be transferred between the input coil and the output coil. The "near equal amount" is the result of imperfections or losses in the transformer causing the efficiency of the same transformer to approach, but never exceed 100%. In the mid 1980's, a researcher by the name of Floyd Sweet developed a breakthrough transformer he called the Space Quanta Modulator (SQM) and later renamed the Vacuum Triode Amplifier (VTA) by researcher, Tom Bearden. The transformer had an efficiency exceeding 1,000,000%. Mainstream physics could not explain how this was possible. Shrouded in secrecy, the operation of Floyd's FREE Energy / Overunity Transformer VTA device was not understood until now. In 2002, an article published in Infinite Energy Magazine authored by D. L. Hotson revealed how the VTA operates utilizing what is called the "Dirac Sea of Negative Energy." The key to understanding how FREE Energy / Overunity transformers work is through the application of a negative work function applied to transformer T1 shown above. This negative work function is created using magnets forced together in an opposing field configuration. The opposing field action causes the magnetic field density B to curl into Dirac COMPLEX space causing the field to become COMPLEX jB. This, in turn, forces the input electric current i SRC to become COMPLEX ji SRC. Because of this action, what is observed on a typical ammeter is a significant reduction of REAL electric current i SRC. Ammeters cannot measure COMPLEX current; therefore, the REAL input current appears to vanish. Given a COMPLEX magnetic field density jB, calculations show the field energy in a given volume V of space becomes negative, which satisfies the negative energy solution of the Dirac Equation,-E. This field is referred to as an electromagnetic dampening field and is present around transformer T1. Since the output power of transformer T1 drives a REAL load R LOAD , the output electric current i LOAD is REAL. Therefore, efficiencies greatly exceeding 100% are measured. This permits the construction of self-sustainable FREE Energy / Overunity devices with phenomenally large observable power gains. This lecture will show how consistent and valid using ordinary classical analysis works at the macro scale as well as at the quantum level. William Alek is President and CEO of AuroraTek, Inc. AuroraTek is dedicated to bringing forth advance and exotic FREE Energy Self-Sustaining Technologies to the world. William is the inventor of the SmartPAK TM / SZT TM FREE Energy / Overunity Energy Management System. William has more than 30 years of experience as an embedded computer hardware, electronic hardware and software engineering consultant, and has a BSEE degree from IIT Chicago, Illinois (1979). William can be contacted at:

After a brief review of the hybrid QM/MM molecular dynamics scheme and its coupling to the metadynamics method, I will show how such a combination of computational tools can be used to study chemical reactions of general biological interest. Specifically, by using such a reactive hybrid paradigm, where the QMdriver is a Car–Parrinello Lagrangian dynamics, we have inspected the ATP hydrolysis reaction in the anti-freezing protein known as heat shock cognate protein (Hsc70) and the unconventional propagation of protons across peptide groups in the H-path of the bovine cytochrome c oxidase. While the former represents a fundamental reaction operated by all living beings in a wealth of processes and functions, the second one is involved in cell respiration. For both systems accurate X-ray data are available, yet the actual reaction mechanism escapes experimental probes. The simulations presented here provide the complementary information missing in experiments, offer a direct insight into the reaction mechanisms at a molecular level, and allow to understand which pathways nature can follow to realize these processes fundamental to living organisms.

Peptide-membrane interactions play an important role in a number of biological pro- cesses, such as antimicrobial defence mechanisms, viral translocation, membrane fu- sion and functions of membrane proteins. In particular, amphipathic α-helical peptides comprise a large family of membrane-active peptides that could exhibit a broad range of biological activities. A membrane, interacting with an amphipathic α-helical pep- tide, may experience a number of possible structural transitions, including stretching, reorganization of lipid molecules, formation of defects, transient and stable pores, for- mation of vesicles, endo- and pinocytosis and other phenomena. Naturally, theoretical and experimental studies of these interactions have been an intense on-going area of research. However, complete understanding of the relationship between the structure of the peptide and the mechanism of interaction it induces, as well as molecular details of this process, still remain elusive. Lack of this knowledge is a key challenge in our efforts to elucidate some of the biological functions of membrane active peptides or to design peptides with tailored functionalities that can be exploited in drug delivery or antimicrobial strategies.

In principle, molecular dynamics is a powerful research tool to study peptide-membrane interactions, which can provide a detailed description of these processes on molecular level. However, a model operating on the appropriate time and length scale is imperative in this description. In this study, we adopt a coarse-grained approach where the accessible simulation time and length scales reach microseconds and tens of nanome- ters, respectively. Thus, the two key objectives of this study are to validate the ap- plicability of the adopted coarse-grained approach to the study of peptide-membrane interactions and to provide a systematic description of these interactions as a function of peptide structure and surface chemistry.

We applied the adopted strategy to a range of peptide systems, whose behaviour has been well established in either experiments or detailed atomistic simulations and outlined the scope and applicability of the coarse-grained model. We generated some useful insights on the relationship between the structure of the peptides and the mechanism of peptide-membrane interactions. Particularly interesting results have been obtained for LS3, a membrane spanning peptide, with a propensity to self-assembly into ion-conducting channels. Firstly, we captured, for the first time, the complete process of self-assembly of LS3 into a hexameric ion-conducting channel and explored its properties. The channel has structure of a barrel-stave pore with peptides aligned along the lipid tails. However, we discovered that a shorter version of the peptide leads to a more disordered, less stable structure often classified as a toroidal pore. This link between two types of pores has been established for the first time and opens interesting opportunities in tuning peptide structures for a particular pore-inducing mechanism. We also established that different classes of peptides can be uniquely characterized by the distinct energy profile as they cross the membrane. Finally, we extended this investigation to the internalization mechanisms of more complex entities such as peptide complexes and nanoparticles. Coarse-grained steered molecular dynamics simulations of these model systems are performed and some preliminary results are presented in this thesis.

To summarize, in this thesis, we demonstrate that coarse-grained models can be successfully used to underpin peptide interaction and self-assembly processes in the pres- ence of membranes in their full complexity. We believe that these simulations can be used to guide the design of peptides with tailored functionalities for applications such as drug delivery vectors and antimicrobial systems. This study also suggests that coarse-grained simulations can be used as an efficient way to generate initial configurations for more detailed atomistic simulations. These multiscale simulation ideas will be a natural future extension of this work.

In the paper, we discuss the usage of constant and fuzzy similarity awards while establishing an optimal alignment between energy characteristics of two compared protein energy profiles. Single protein energy profile is a set of energy characteristics of various types of energy. The energy profile is determined for a given protein structure. We use these profiles to find protein molecules of the same structural protein family and inspect conformational modifications in their molecular structures as an effect of biochemical reactions or environmental influences. Energy profiles are received in the computational process based on the molecular mechanics theory. Afterwards, these profiles can be stored in the special purpose database (EDB) and used by the search engine to find similar fragments of protein structures on the energy level. To optimize the alignment path we use modified, energy-adapted Smith-Waterman method with one of the tested similarity awards.

Hydrogen dissociation and recombination is considered to be an energy transfer mechanism only. The process proposed herein may provide a promising new direction for new energy research. Theoretical explanation for high efficiency of such physical systems is proposed for the first time in the present work.

We demonstrate an extensible flat-histogram Monte Carlo simulation methodology for studying the adsorption of multicomponent fluids in flexible porous solids. This methodology allows us to easily obtain the complete free energy landscape for the confined fluid-solid system in equilibrium with a bulk fluid of any arbitrary composition. We use this approach to study the adsorption of a prototypical coarse-grained binary fluid in “Hookean” solids, where the free energy of the solid may be described as a simple spring. However, our approach is fully extensible to solids with arbitrarily complex free energy profiles. We demonstrate that by tuning the fluid-solid interaction ranges, the inhomogeneous fluid structure inside the pore can give rise to enhanced selective capture of a larger species through cooperative adsorption with a smaller one. The maximum enhancement in selectivity is observed at low to intermediate pressures and is especially pronounced when the larger species is very dilute in the bulk. This suggest a mechanism by which the selective capture of a minor component from a bulk fluid may be enhanced.

We present a first principles study of the Ziegler−Natta MgCl2-supported polymerization of ethylene in the framework of the Car-Parrinello approach. In particular we investigate the titanium active sites on the (110) surface of the support focusing on Corradini's model and the possible alternative configurations. We find that different catalyst sites are allowed and that the relevant energetics as well as the reactivity in the alkyl chain formation process strongly depend on the local geometry. During deposition of TiCl4 and complex formation, which are energetically downhill, the dynamical approach allows us to follow the reaction pathway in an unbiased way. By means of Car−Parrinello constrained molecular dynamics we then determine the free energy profiles and estimate activation barriers in the alkene insertion processes. Furthermore a dynamical study of the insertion of a second ethylene molecule offers an interesting insight into the chain growth process and the stereochemical character of the polymer, providing a complete picture of the reaction mechanism.

Advanced oxidation processes (AOPs) are commonly used for treating recalcitrant wastewater with varying degree of efficiency, depending on several operating parameters. In this review, a comparative study among selected AOPs integrated with ultraviolet (UV) (UV/Fenton, UV/H2O2, UV/O-3, UV/TiO2, UV/persulfate, UV/H2O2/O-3, and UV/TiO2/H2O2) was conducted. The cost implication, changes in kinetics, changes in reaction rates, and effects of various parameters such as type of contaminants, pH, catalyst loading concentration of oxidants, and type of UV light are explained and concluded in this paper. From this review, it is concluded that UV-integrated AOPs are efficient for wastewater treatment. However, a few aspects must be considered including process scale-up, kinetics of combined processes, reactor configuration, modeling of a system, and optimization of operating parameters to enhance the process efficiency.

Link to full text articles :
http://www.degruyter.com/view/j/revce.2015.31.issue-3/revce-2014-0039/revce-2014-0039.xml

The photoswitching speed of the reversibly switchable fluorescent proteins (RSFPs) from the family of green fluorescent proteins (GFPs) changes upon mutation which is of direct importance for various high-resolution techniques. Dronpa is one of the most used RSFPs. Its point mutants rsFastLime (Dronpa V157G) and rsKame (Dronpa V157L) exhibit a striking difference in their photoswitching speed. Here the QM/MM on-the-fly string method is used in order to explore the details of the thermal isomerization mechanism. The four principal ways in which isomerization may occur have been scrutinized for each of the three proteins. It has been shown that thermal isomerization occurs via a one-bond-flip mechanism in all three proteins, although, in rsKame, where the chromophore is constrained more, the activation free energy difference between hula-twist and one-bond-flip is significantly smaller. Functional mode analysis has been applied to examine the motions of the amino acids during the isom...

Understanding the nature of the free-energy surfaces for phosphate hydrolysis is a prerequisite for understanding the corresponding key chemical reactions in biology. Here, the challenge has been to move to careful ab initio QM/MM (QM(ai)/MM) free-energy calculations, where obtaining converging results is very demanding and computationally expensive. This work describes such calculations, focusing on the free-energy surface for the hydrolysis of phosphate monoesters, paying special attention to the comparison between the one water (1W) and two water (2W) paths for the proton-transfer (PT) step. This issue has been explored before by energy minimization with implicit solvent models and by nonsystematic QM/MM energy minimization, as well as by nonsystematic free-energy mapping. However, no study has provided the needed reliable 2D (3D) surfaces that are necessary for reaching concrete conclusions. Here we report a systematic evaluation of the 2D (3D) free-energy maps for several relevant systems, comparing the results of QM(ai)/MM and QM(ai)/implicit solvent surfaces, and provide an advanced description of the relevant energetics. It is found that the 1W path for the hydrolysis of the methyl diphosphate (MDP) trianion is 6–9 kcal/mol higher than that the 2W path. This difference becomes slightly larger in the presence of the Mg2+ ion because this ion reduces the pKa of the conjugated acid form of the phosphate oxygen that accepts the proton. Interestingly, the BLYP approach (which has been used extensively in some studies) gives a much smaller difference between the 1W and 2W activation barriers. At any rate, it is worth pointing out that the 2W transition state for the PT is not much higher that the common plateau that serves as the starting point of both the 1W and 2W PT paths. Thus, the calculated catalytic effects of proteins based on the 2W PT mechanistic model are not expected to be different from the catalytic effects predicted using the 1W PT mechanistic model, which was calibrated on the observed barrier in solution and in which the TS charge distribution was similar to the that of the plateau (as was done in all of our previous EVB studies).

A method to compute the interfacial excess free energy of systems where a liquid phase is interacting with a solid phase is presented. The calculations are carried out by means of molecular dynamics simulations. The algorithm is based on a thermodynamic integration scheme that reversibly turns a flexible atomistically detailed solid surface that interacts with a liquid phase into a flat surface and allows the calculation of the variation in Gibbs free energy. The approach is probed by applying it to a model system of Lennard–Jones particles and comparing to previous calculations on similar systems.

We study the generation of a dinuclear Fe(IV)oxo species, [EDTAH·FeO·OFe·EDTAH](2-), in aqueous solution at room temperature using Density Functional Theory (DFT) and Ab Initio Molecular Dynamics (AIMD). This species has been postulated as an intermediate in the multi-step mechanism of autoxidation of Fe(II) to Fe(III) in the presence of atmospheric O(2) and EDTA ligand in water. We examine the formation of [EDTAH·FeO·OFe·EDTAH](2-) by direct cleavage of O(2), and the effects of solvation on the spin state and O-O cleavage barrier. We also study the reactivity of the resulting dinuclear Fe(IV)oxo system in CH(4) hydroxylation, and its tendency to decompose to mononuclear Fe(IV)oxo species. The presence of the solvent is shown to play a crucial role, determining important changes in all these processes compared to the gas phase. We show that, in water solution, [EDTAH·FeO·OFe·EDTAH](2-) (as well as its precursor [EDTAH·Fe·O(2)·Fe·EDTAH](2-)) exists as stable species in a S = 4 ground spin state when hydrogen-bonded to a single water molecule. Its structure comprises two facing Fe(IV)oxo groups, in an arrangement similar to the one evinced for the active centre of intermediate Q of soluble Methane Monooxygenase (sMMO). The inclusion of the water molecule in the complex decreases the overall symmetry of the system, and brings about important changes in the energy and spatial distribution of orbitals of the Fe(IV)oxo groups relative to the gas phase. In particular, the virtual 3σ* orbital of one of the Fe(IV)oxo groups experiences much reduced repulsive orbital interactions from ligand orbitals, and its consequent stabilisation dramatically enhances the electrophilic character of the complex, compared to the symmetrical non-hydrated species, and its ability to act as an acceptor of a H atom from the CH(4) substrate. The computed free energy barrier for H abstraction is 28.2 kJ mol(-1) (at the BLYP level of DFT), considerably below the gas phase value for monomeric [FeO·EDTAH](-), and much below the solution value for the prototype hydrated ferryl ion [FeO(H(2)O)(5)](2+).

Various reaction pathways and corresponding activation barriers in the initial oxidation of Si(100) surfaces are clarified by free-energy sampling techniques combined with the Car-Parrinello molecular dynamics. We find a crucial stable geometry which is ubiquitous during the oxidation and links the dissociation of O 2  molecules and the oxidation of subsurfaces. The calculated free-energy landscape provides a comprehensive picture of the various competing reaction pathways.

The enzyme biotin carboxylase (BC) uses adenosine triphosphate (ATP) to carboxylate biotin and is involved in fatty acid synthesis. Structural evidence suggests that the B domain of BC undergoes a large hinge motion of ∼45° when binding and releasing substrates. Escherichia coli BC can function as a natural homodimer and as a mutant monomer. Using molecular dynamics simulations, we evaluate the free energy profile along a closure angle of the B domain of E. coli BC for three cases: a monomer without bound Mg2ATP, a monomer with bound Mg2ATP, and a homodimer with bound Mg2ATP in one subunit. The simulation results show that a closed state is the most probable for the monomer with or without bound Mg2ATP. For the dimer with Mg2ATP in one of its subunits, communication between the two subunits was observed. Specifically, in the dimer, the opening of the subunit without Mg2ATP caused the other subunit to open, and hysteresis was observed upon reclosing it. The most stable state of the dimer is one in which the B domain of both subunits is closed; however, the open state for the B domain without Mg2ATP is only approximately 2kBT higher in free energy than the closed state. A simple diffusion model indicates that the mean times for opening and closing of the B domain in the monomer with and without Mg2ATP are much smaller than the overall reaction time, which is on the order of seconds.

Peptide-membrane interactions play an important role in a number of biological processes, such as antimicrobial defence mechanisms, viral translocation, membrane fusion and functions of membrane proteins. In particular, amphipathic α-helical peptides comprise a large family of membrane-active peptides that could exhibit a broad range of biological activities. A membrane, interacting with an amphipathic α-helical peptide, may experience a number of possible structural transitions, including stretching, reorganization of lipid molecules, formation of defects, transient and stable pores, formation of vesicles, endoand pinocytosis and other phenomena. Naturally, theoretical and experimental studies of these interactions have been an intense on-going area of research. However, complete understanding of the relationship between the structure of the peptide and the mechanism of interaction it induces, as well as molecular details of this process, still remain elusive. Lack of this knowledg...

ABSTRACT Experiments and molecular dynamics calculations have shown that cavitand I has a bimodal selectivity for alkali ions in water saturated CHCl3 (experiment) and water (simulations). In this paper, molecular dynamics and free energy perturbation calculations are used to study the selectivity of I for alkali ions in methanol. The calculations predict that Cs+ is bound tightest by I, the same as in water. As previously predicted, the bimodal selectivity disappears in methanol. This change in specificity is caused by a change in the number of stabilizing interactions in which solvent molecules that accompany the alkali ion into the cavity of I can participate.

The energetics of B-DNA bending toward the major and minor grooves were quantified by free energy simulations at four different KCl concentrations. Increased [KCl] led to more flexible DNA, with persistence lengths that agreed well with experimental values. At all salt concentrations, major groove bending was preferred, although preferences for major and minor groove bending were similar for the A-tract containing sequence. Since the phosphate repulsions and DNA internal energy favored minor groove bending, the preference for major groove bending was thought to originate from differences in solvation. Water in the minor groove was tighter bound than water in the major groove, and harder to displace than major groove water, which favored the compression of the major groove upon bending. Higher [KCl] decreased the persistence length for both major and minor groove bending but did not greatly affect the free energy spacing between the minor and major groove bending curves. For sequences without A-tracts, salt affected major and minor bending to nearly the same degree, and did not change the preference for major groove bending. For the A-tract containing sequence, an increase in salt concentration decreased the already small energetic difference between major and minor groove bending. Since salts did not significantly affect the relative differences in bending energetics and hydration, it is likely that the increased bending flexibilities upon salt increase are simply due to screening.

Experiments and molecular dynamics calculations have shown that cavitand I has a bimodal selectivity for alkali ions in water saturated with CHCL3(experiment) and water (simulations).  In this paper, molecular dynamics and free energy perturbation calculations are used to study the selectivity of I for alkali ions in methanol.  The calculations predict that Cs+ is bound tightest by I, the same as in water.  As previously predicted, the biomodal selectivity disappears in methanol.  This change in specificity is caused by a change in the number of stabilizing interactions in which solvent molecules that accompany the alkali ion into the cavity of I can participate.

Articles you may be interested in Combining ab initio quantum mechanics with a dipole-field model to describe acid dissociation reactions in water: First-principles free energy and entropy calculations J. Chem. Phys. 132, 074112 (2010); 10.1063/1.3317398 Ab initio molecular dynamics calculations of ion hydration free energies J. Chem. Phys. 130, 204507 (2009); 10.1063/1.3137054 Calculating solution redox free energies with ab initio quantum mechanical/molecular mechanical minimum free energy path method J. Chem. Phys. 130, 164111 (2009); 10.1063/1.3120605 Probing protein environment in an enzymatic process: All-electron quantum chemical analysis combined with ab initio quantum mechanical/molecular mechanical modeling of chorismate mutase J. Chem. Phys. 129, 125105 (2008); 10.1063/1.2977458 Parallel iterative reaction path optimization in ab initio quantum mechanical/molecular mechanical modeling of enzyme reactions Energy and free energy barriers for acetaldehyde conversion in aldehyde oxidoreductase are determined for three reaction pathways using quantum mechanical/molecular mechanical QM/ MM calculations on the solvated enzyme. Ab initio single-point QM/MM energies are obtained at the stationary points optimized at the DFTB3LYP/MM level. These ab initio calculations employ local correlation treatments LMP2 and LCCSDT0 in combination with augmented triple-and quadruple-zeta basis sets, and the final coupled cluster results include MP2-based corrections for basis set incompleteness and for the domain approximation. Free energy perturbation FEP theory is used to generate free energy profiles at the DFTB3LYP/MM level for the most important reaction steps by sampling along the corresponding reaction paths using molecular dynamics. The ab initio and FEP QM/MM results are combined to derive improved estimates of the free energy barriers, which differ from the corresponding DFTB3LYP/MM energy barriers by about 3 kcal mol −1. The present results confirm the qualitative mechanistic conclusions from a previous DFTB3LYP/MM study. Most favorable is a three-step Lewis base catalyzed mechanism with an initial proton transfer from the cofactor to the Glu869 residue, a subsequent nucleophilic attack that yields a tetrahedral intermediate IM2, and a final rate-limiting hydride transfer. The competing metal center activated pathway has the same final step but needs to overcome a higher barrier in the initial step on the route to IM2. The concerted mechanism has the highest free energy barrier and can be ruled out. While confirming the qualitative mechanistic scenario proposed previously on the basis of DFTB3LYP/MM energy profiles, the present ab initio and FEP QM/MM calculations provide corrections to the barriers that are important when aiming at high accuracy.

The peptide group connecting Tyr440 and Ser441 of the bovine cytochrome c oxidase is involved in a recently proposed proton-transfer path (H-path) where, at variance with other pathways (D- and K-paths), a usual hydrogen-bond network is interrupted, thus making this proton propagation rather unconventional. Our density-functional based molecular dynamics simulations show that, despite this anomaly and provided that a proton can reach a nearby water, a multistep proton-transfer pathway can become a viable pathway for such a reaction:  A proton is initially transferred to the carbonyl oxygen of a keto form of the Tyr440-Ser441 peptide group [−CO−NH−], producing an imidic acid [−C(OH)−NH−] as a metastable state; the amide proton of the imidic acid is then transferred, spontaneously to the deprotonated carboxyl group of the Asp51 side chain, leading to the formation of an enol form [−C(OH)N−] of the Tyr440-Ser441 peptide group. Then a subsequent enol-to-keto tautomerization occurs via a double proton-transfer path realized in the two adjacent Tyr440-Ser441 and Ser441-Asp442 peptide groups. An analysis of this multistep proton-transfer pathway shows that each elementary process occurs through the shortest distance, no permanent conformational changes are induced, thus preserving the X-ray crystal structure, and the reaction path is characterized by a reasonable activation barrier.

Aminoadamantane derivatives, such as amantadine and rimantadine, have been reported to block the M2 membrane protein of influenza A virus (A/M2TM), but their use has been discontinued due to reported resistance in humans. Understanding the mechanism of action of amantadine derivatives could assist the development of novel potent inhibitors that overcome A/M2TM resistance. Here, we use Free Energy Perturbation calculations coupled with Molecular Dynamics simulations (FEP/MD) to rationalize the thermodynamic origin of binding preference of several aminoadamantane derivatives inside the A/M2TM pore. Our results demonstrate that apart from crucial protein–ligand intermolecular interactions, the flexibility of the protein, the water network around the ligand, and the desolvation free energy penalty to transfer the ligand from the aqueous environment to the transmembrane region are key elements for the binding preference of these compounds and thus for lead optimization. The high correlation of the FEP/MD results with available experimental data (R2 = 0.85) demonstrates that this methodology holds predictive value and can be used to guide the optimization of drug candidates binding to membrane proteins.

We present molecular dynamics simulations of dimyristoylphosphatidylcholine (DMPC) lipid bilayers in the presence of dimethyl sulfoxide (DMSO). The MD simulations focus on understanding the effect of 3 mol % DMSO on structural and permeation properties of DMPC bilayers. The potential of mean force (PMF) and the diffusivity profiles along the normal direction to the bilayer were calculated for water and DMSO molecules in systems containing 0 and 3 mol % DMSO. The simulation results indicate that while the presence of DMSO has only a small effect on diffusion coefficients of both water and DMSO molecules, it affects significantly the corresponding trans-membrane free energy profiles. Using the free energy profiles and diffusivities for water and DMSO and by employing an inhomogeneous solubility-diffusion model we calculated the permeability coefficients. Our simulations show that the increase of the concentration of DMSO in the solution to 3 mol % leads to a significant increase, by about 3 times, of the permeability of water through a DMPC bilayer; a permeability increase that might explain in part the unusual ability of DMSO, even at relatively low concentrations, to reduce the osmotic pressure imbalance present during cryopreservation protocols.