PubMed HealthSearch

SEARCH · PubMed Health

Results for “Compaction simulator”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

Phylogenetic Methods Meet Deep Learning.

Deep learning (DL) has been widely used in various scientific fields, but its integration into phylogenetics has been slower, primarily due to the complex nature of phylogenetic data. The studies that apply DL to sequencing data often limit analyses to four-taxon trees. Many of these studies serve as "proof of principle" and perform similarly to traditional phylogeny reconstruction methods. New ways of using training data, such as encoding with compact bijective ladderized vectors or transformers, enable the handling of much larger trees and genomic data sets. This short perspective focuses on the application of DL in phylogenetics, introducing prevalent DL architectures. We highlight potential problems in the field by discussing the risks of using simulation-based training data and emphasize the importance of reproducibility and robustness in computational estimates. Finally, we explore promising research areas, including the combination of phylogenetics and population genetics in DL, the analysis of neighbor dependencies, and the potential to significantly reduce computational cost compared to traditional methods. This perspective illustrates the potential of DL in complementing traditional phylogeny reconstruction methods and aiding the advancement of phylogenetic analysis, especially in performing computationally demanding tasks such as model selection or estimating branch support values.

Humans

First-principles calculation of the folding free energy of a three-helix bundle protein.

The folding and unfolding of a three-helix bundle protein were explored with molecular-dynamics simulations, cluster analysis, and weighted-histogram techniques. The folding-unfolding process occurs by means of a "folding funnel," in which a uniform and broad distribution of conformational states is accessible outside of the native manifold. This distribution narrows near a transition region and becomes compact within the native manifold. Key thermodynamic steps in folding include initial interactions around the amino-terminal helix-turn-helix motif, interactions between helices I and II, and, finally, the docking of helix III onto the helix I-II subdomain. A metastable minimum in the calculated free-energy surface is observed at approximately 1.5 times the native volume. Folding-unfolding thermodynamics are dominated by the opposing influences of protein-solvent energy, which favors unfolding, and the overall entropy, which favors folding by means of the hydrophobic effect.

Amino Acid Sequence

Map formation in proprioceptive cortex.

Current understanding of feature maps in proprioceptive cortex is quite limited. To complement experimental studies, we developed a computational model of map formation in proprioceptive cortex. Muscle length and tension from six muscle groups controlling the position of a model arm in three-dimensional space served as input to the simulated cortex. The resultant feature map consisted of regularly spaced clusters of cortical columns representing individual muscle lengths and tensions. Cortical units became tuned to plausible combinations of tension and length, and multiple representations of each muscle group were present. The map was organized such that compact regions within which all muscle group lengths and tensions are represented could be identified. Most striking was the observation that, although not explicitly present in the input, the cortical map developed a representation of the three-dimensional space in which the arm moved. These findings represent testable predictions about proprioceptive cortex, and may also help clarify some organizational issues concerning primary motor cortex.

Arm

Solution structure of recombinant hirudin and the Lys-47----Glu mutant: a nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study.

The solution structure of recombinant wild-type hirudin and of the putative active site mutant Lys-47----Glu has been investigated by nuclear magnetic resonance (NMR) spectroscopy at 600 MHz. The 1H NMR spectra of the two hirudin variants are assigned in a sequential manner with a combination of two-dimensional NMR techniques. Some assignments made in our previous paper [Sukumaran, D. K., Clore, G. M., Preuss, A., Zarbock, J., & Gronenborn, A. M. (1987) Biochemistry 26, 333-338] were found to be incorrect and are now corrected. Analysis of the NOE data indicates that hirudin consists of an N-terminal compact domain (residues 1-49) held together by three disulfide linkages and a disordered C-terminal tail (residues 50-65) which does not fold back on the rest of the protein. This last observation corrects conclusions drawn by us previously on hirudin extracted from its natural source, the leech Hirudo medicinalis. The improved sensitivity of the 600-MHz spectrometer relative to that of our old 500-MHz spectrometer, the availability of two variants with slightly different chemical shifts, and the additional information arising from stereospecific assignments of methylene beta-protons and methyl protons of valine have permitted the determination of the solution structure of hirudin with much greater precision than before. Structure calculations on the N-terminal domain using the hybrid distance geometry-dynamical simulated annealing method were based on 685 and 661 approximate interproton distance restraints derived from nuclear Overhauser enhancement (NOE) data for the wild-type and mutant hirudin, respectively, together with 16 distance restraints for 8 backbone hydrogen bonds identified on the basis of NOE and amide NH exchange data and 26 phi backbone and 18 chi 1 side-chain torsion angle restraints derived from NOE and three-bond coupling constant data. A total of 32 structures were computed for both the wild-type and mutant hirudin. The structure of residues 2-30 and 37-48 which form the core of the N-terminal domain is well determined in both cases with an average atomic rms difference between the individual structures and the respective mean structures of approximately 0.7 A for the backbone atoms and approximately 1 A for all atoms. As found previously, the orientation of the exposed finger of antiparallel beta-sheet (residues 31-36) with respect to the core could not be determined on the basis of the present data due to the absence of any long-range NOEs between the exposed finger and the core.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Numerical instabilities in bone remodeling simulations: the advantages of a node-based finite element approach.

Long bone structure occurs in two distinct forms. The bone mass near the joint is primarily found in a distributed, porous trabecular structure, while in the diaphyses a tubular cortical structure is formed. It seems likely that these two observed morphologies come about, at least in part, as a mechanical adaptation to the different mechanical demands in the two regions. Mathematical formulations of this dependency have been proposed, thus facilitating numerical simulations of bone adaptation. Recently two types of discontinuities have been observed in these simulations. The first type (near-field) appears in areas near distributed load application and is characterized by a 'checkerboard' pattern of density wherein adjacent remodeled elements alternate between low and high density. The second type of discontinuity (far-field) appears remote from the load application and is characterized by strut or column-like regions of elements which become fully compact bone while adjacent regions are fully resorbed. In fact, the far-field discontinuity is an accurate representation of bone physiology and morphology since it is consistent with the appearance of cortical bone in the diaphysis. On the other hand, the near-field discontinuity, appears in a region where continuous distributions of intermediate apparent densities (trabecular bone) are expected. This finding may cause some to question whether a single continuum formulation of bone remodeling can predict both discontinuous far-field behavior and continuous near-field behavior. We describe a node-based implementation of current continuum bone remodeling theories which eliminates the spurious near-field discontinuities and preserves the anatomically correct far-field discontinuities, thus indicating that a single biological process may be at work in forming and maintaining both far-field and near-field morphologies.

Algorithms

Crystal structure of recombinant human interleukin-4.

The crystal structure of recombinant human interleukin-4 (rhuIL-4) was initially determined at 3.5-A resolution by multiple isomorphous replacement techniques and subsequently refined to a resolution of 2.35 A by simulated annealing. The final crystallographic R-factor, based on all data in the range 6.0-2.35 A (7470 reflections), is 0.232. Bond lengths and bond angles in the molecule have root mean square deviations from ideal values of 0.016 A and 2.4 degrees, respectively. The overall structure is highly compact and globular with a predominantly hydrophobic core. The main structural feature of rhuIL-4 is a four alpha-helix bundle, which composes approximately 58% of the structure. The helices are arranged in a left-handed antiparallel bundle with two overhand connections. Within these connections is a two-stranded antiparallel beta-sheet. Both the tertiary and secondary structures of rhuIL-4 are similar to those of human granulocyte-macrophage colony-stimulating factor. Critical regions for receptor binding are proposed.

Amino Acid Sequence

The finite element analysis of brain oedema associated with intracranial meningiomas.

The mathematical model of vasogenic brain oedema, which was presented at the previous meeting in 1987, was applied to the analysis of peritumoural brain oedema associated with meningiomas. Magnetic resonance images of 90 patients with intracranial meningiomas were reviewed to analyze the spatial extension of peritumoural brain oedema. It is assumed that the heterogeneous pattern of distribution of peritumoural oedema reflects the variability of the compact density of the fibers in the white matter. A two dimensional finite element model was constructed with 786 triangular elements from a horizontal section of the human brain. The development of oedema, the change of interstitial pressure, the deformation of the brain and the absorption of oedema fluid could be simulated by the finite element method. The result of computer simulation represented interactive behaviour of the brain tissue, extracellular fluid, and cerebrospinal fluid in the clinical situation. The finite element method (FEM) may provide a new experimental tool to analyze the pathophysiology of vasogenic brain oedema.

Brain

Uniform regional heating of the lower trunk: numerical evaluation of tumor temperature distributions.

The temperature distributions in deep seated tumors resulting from uniform heating of the abdominal and pelvic regions of the trunk are predicted from a one dimensional numerical solution of the bio-heat transfer equation. The effect of tumor size and location are investigated for two tumor perfusion models: uniform perfusion and a concentric annulus perfusion model. Tumor temperature distributions are considered acceptable if the range of temperatures in the tumor lie between 42 degrees C and 60 degrees C. This range of tumor temperatures is defined as Tave +/- 2 sigma where sigma is the population standard deviation of tumor temperatures from the average computed at the nodal points in the finite difference array. To simulate practical clinical restrictions, muscle and fat temperatures are not allowed to exceed 44 degrees C, significant portions of the viscera are not allowed to exceed 42 degrees C, and the total absorbed power required to maintain steady state cannot exceed two kilowatts. Over 100 possible cases are presented in a compact form. From this study it appears that heating systems with power deposition patterns approximately uniform are promising for heating deep-seated tumors. Small, detectable tumors (approximately 2 cm in size) are adequately heated for a wider range of conditions than are larger tumors. Excessively high temperatures in deep-seated, normal tissue could be a significant limitation for this technique.

Abdominal Neoplasms

Computer simulation of neuronal circuit models of rhythmic behavior in the electroencephalogram.

A computer program for modeling some features of the electroencephalogram (EEG) recorded by scalp electrodes in terms of the time- and space-dependent interactions of populations of neurons in different hypothetical brain configurations was developed. The input of the model consists of: (1) geometric and anatomic data characterizing the brain configuration; (2) physiologic features characterizing neurons; and (3) functions describing the time-dependent afferent impulses to the brain configuration under study. The output of the model consists of plots of selected intracellular and extracellular potentials as a function of time. In application of the model to various brain configurations, some configurations were sufficiently compact spatially that propagation times of action potentials between elements were either taken to be constant or were nearly independent of distance within the accuracy of the calculations. Other configurations represented cerebral cortex alone or a combined thalamocortical system in which many elements interacted via global interconnections. The basic requirement for rhythmic behavior is the existence of circuits containing inhibitory neurons. The characteristic frequencies of rhythmic oscillations are primarily determined by the local circuit parameters and are relatively independent of global circuit parameters.

Action Potentials

A highly simplified horizontal electrophoretic apparatus including a handmade power supply and its application.

An extremely simplified electrophoretic apparatus and power supply have been introduced for horizontal (flat-bed) electrophoresis and isoelectrofocusing. The electrophoretic apparatus consisted of a buffer tray with a plastic food container in which a gel glass plate attached to two removable bar electrodes with rubber bands was submerged. The removable bar electrode consisted of an acrylic bar plate containing holes to which platinum wire was attached. The power supply simply contained a bridge diode, fuse, capacitor, and output terminals which were also assembled in a small plastic food container. Since the output electric potential of the power supply was constant pulse dc 90 V (in the absence of a capacitor) or 140 V (in the presence of a capacitor) at 100 V ac input, the following equation was experimentally derived to control the electrophoretic current: I (mA) = aD + b, I (mA) = kF. In these, I, a, D, k, and F were electrophoretic current, constant, distance between positive and negative electrodes, constant, and dilution factor of the electrophoretic buffer which was proportional to buffer concentration, respectively. These equations indicate that electrophoretic current can be controlled by the changes of electrode distance and buffer dilution. The latter equation was theoretically derived from the theory of electrolyte conductance and Ohm's law and was simulated with a microcomputer. With the apparatus and power supply, agarose gel electrophoresis of DNA and discontinuous polyacrylamide gel electrophoresis of protein samples were successfully carried out. The construction and assembly of the system can be easily carried out in a laboratory without any special tools and machines. The high cost performance, compactness, and simplicity were superior points of this system. The applicability of the equation I = kF to tube gel and vertical slab gel electrophoresis was tested. The rheostat usage made it easy for the power supply to change dc-output potential without spoiling its cost performance. A convenient sample slot-former and gel preparation with it are also described.

Computers

[The level of the musical loud sound and noise induced hearing impairment].

Recently, there has been an increasing number of reports concerning hearing impairment which musical loud sound is thought to be one of the causes. We are getting more of this musical loud sound as cassette tape recorders with head phones such as Walkman and so forth get popular as well as occasions to attending rock concerts and going to discotheques increase. This hearing impairment is generally called discotheque deafness and the following three types are considered; 1) deafness which have fixed by accumulation of loud sound over a long period of time as seen in people involved in musical performance such as rock musicians and mixing engineers; 2) abrupt noise induced hearing impairment triggered by loud sound and 3) state of deafness which is a progressing stage towards recovery of noise induced temporary threshold shift (NITTS), which occurs temporarily by a loud sound stimulus, and hearing ability recovers afterward. However, it is considered that these musical loud sounds not only changes every moment according to method of performing or type of music, but the volume of the sound actually reaching the auditory sense differs largely by locations and direction of the ear and speakers. So it becomes necessary to measure the accumulation of the noise which each individual is exposed under over a long period of time and at the same time carry out the regular medical checkups including hearing test to check the initiation and advancement of the noise induced hearing impairment. Then we can examine the relationship between loudness of the environmental noise and initiation and advancement of the hearing impairment. However, there has not been a device which is compact and measures noise exposure individually over a long period of time. So we have experimentally produced ultra compact noise dosimeter which we named Noise Badge, and with it we actually measured individual noise exposure over a long time in rock music, noise in discotheque and noisy factory. Then we examined the relationship between these loud sound and noise induced temporary threshold shift (NITTS) in discotheques and noise proof room using simulation of loud sound exposure. Moreover, we measured the most comfortable loudness level of head phones in each examine and different types of music with environmental noise in consideration, thus examining the relationship between musical loud sound and the hearing impairment.

Adaptation, Physiological

Molecular mechanics of the formation of cholic acid micelles.

The molecular mechanics of cholic acid micelle formation were simulated using the Sybyl energy minimization program (MAXIMIN2), developed by Tripos Associates, interfaced with micro-Vax. Before energy minimization, the molecular dimensions of the cholic acid dodecamer C24H40O6, in terms of the unit cell axes a, b, and c in the cubic crystal class, had values of 13, 18, and 6.7 A, respectively. After energy minimization, at 9370 kcals/dodecamer, these values had increased to 21.6, 42.8 and 20.9 A. At an energy minimization level of 21,626 kcals/dodecamer, the micelle structure is stabilized by hydrophobic interaction, forming distinct horizontal channels along the b-axis, directing the carboxyl and hydroxyl groups toward the surface. These structural changes remain relatively constant as the process of energy minimization continues, down to the lowest energy level we considered, 9370 kcals/dodecamer. The cholic acid layers are highly dissimilar, forming channels of irregular size and shape in a somewhat helical structure. The carboxyl groups and phenanthrene rings are in a puckered orientation, which permits compact packing of the sandwiched multilayers. From the dimension of the channels, it is apparent that guest molecules, such as phospholipid, cholesterol, or inorganic calcium, can be incorporated into the micelle through more than one channel, forming inclusion complexes, such as gallstones.

Cholic Acid

The structure of an RNA pseudoknot that causes efficient frameshifting in mouse mammary tumor virus.

The structure of a 34-nucleotide RNA pseudoknot that causes efficient -1 frameshifting in the messenger RNA of mouse mammary tumor virus has been investigated by NMR. Spectral assignment of the pseudoknot was facilitated by comparative NMR studies on the pseudoknot and on two smaller hairpin RNAs, and by using selective 13C labeling and 13C-edited NMR techniques. The three-dimensional structure of the pseudoknot has been determined. The frameshifter pseudoknot possesses structural features not observed in previously reported model pseudoknots. It has a compact structure with a pronounced bend at the junction of its G.C-rich stems. A single adenylate residue is intercalated between the two stems so that direct coaxial staking of the stems is not possible. The lack of an opposing nucleotide for the stacked, intervening adenylate creates a hinge in the pseudoknot. Most of the loop nucleotides are restrained by base staking interactions which keep the loops from adopting extended conformations. The sterically constrained loops direct the bending of the pseudoknot at the stem-stem junction. The roles of the intercalated adenylate and loop lengths in causing bending can explain their requirement for efficient frameshifting. Our NMR data also indicate that there are internal dynamics associated with the pseudoknot. The unique, compact structure and conformational flexibility of the pseudoknot may be required for recognition and favourable interaction with the translating ribosome, or with translation factors associated with the ribosome.

Base Sequence

Computer graphics with computerized tomography for functional neurosurgery.

A computer graphics technique for computer-assisted stereotactic surgery is presented. The program is designed to aid the surgeon by presenting an on-line graphics display of stereotactic probes and electrodes superimposed on cross sections of the human brain stem. This technique simulates an otherwise blind surgical procedure on a graphics screen for use during surgery. An earlier system based around the DEC MINC-11 BA computer system has been used by the authors for the performance of stereotactic surgery with conventional ventriculography. This system has been upgraded and is now configured about an even more compact microprocessor-based hardware system with expanded graphics capabilities, which also allows its use with computerized tomography.

Brain Diseases

Dynamic Monte Carlo simulations of a new lattice model of globular protein folding, structure and dynamics.

A long-standing problem of molecular biology is the prediction of globular protein tertiary structure from the primary sequence. In the context of a new, 24-nearest-neighbor lattice model of proteins that includes both alpha and beta-carbon atoms, the requirements for folding to a unique four-member beta-barrel, four-helix bundles and a model alpha/beta-bundle have been explored. A number of distinct situations are examined, but the common requirements for the formation of a unique native conformation are tertiary interactions plus the presence of relatively small (but not irrelevant) intrinsic turn preferences that select out the native conformer from a manifold of compact states. When side-chains are explicitly included, there are many conformations having the same or a slightly greater number of side-chain contacts as in the native conformation, and it is the local intrinsic turn preferences that produce the conformational selectivity on collapse. The local preference for helix or beta-sheet secondary structure may be at odds with the secondary structure ultimately found in the native conformation. The requisite intrinsic turn populations are about 0.3% for beta-proteins, 2% for mixed alpha/beta-proteins and 6% for helix bundles. In addition, an idealized model of an allosteric conformational transition has been examined. Folding occurs predominantly by a sequential on-site assembly mechanism with folding initiating either at a turn or from an isolated helix or beta-strand (where appropriate). For helical and beta-protein models, similar folding pathways were obtained in diamond lattice simulations, using an entirely different set of local Monte Carlo moves. This argues strongly that the results are universal; that is, they are independent of lattice, protein model or the particular realization of Monte Carlo dynamics. Overall, these simulations demonstrate that the folding of all known protein motifs can be achieved in the context of a single class of lattice models that includes realistic backbone structures and idealized side-chains.

Algorithms

Some theoretical considerations regarding the effects of steric hindrance and intrinsic global coupling on the flexibility of Fc-anchored immunoglobulins.

Nanosecond fluorescence depolarization studies reported in the accompanying companion paper showed that the long rotational correlation time, phi L, increased somewhat when rabbit IgG anti-dansyl antibodies were anchored in staphylococcal protein A (SpA) soluble complexes. The increases in phi L upon anchoring IgG probably resulted from "global coupling" effects caused by: increased steric hindrance of the antibody segments in the SpA complexes and intrinsic structural constraints already present in the monomeric IgG. Global coupling results from a restriction in the angular range of a flexible segment and is manifest when flexible motions alone cannot depolarize all of the fluorescence, so that the slower global tumbling of the entire particle is also required. Such effects cannot be resolved directly from experimental anisotropy data, however, because only a single long correlation time, phi L, is well defined over the limited time range of most fluorophores. In this paper, estimates of the anisotropy contributions from flexible and global motions of the IgG-SpA complexes are determined by contrasting theoretical and measured decays. For this analysis it was assumed that each of the experimental phi L-values is a weighted composite of the rotational correlation time associated with the less restricted flexible motions of the Fab arms, phi F, and the correlation time associated with global tumbling of the entire particle, phi G. A general two-exponential expression was used to relate phi F and phi G to phi L. This approach was meaningful because phi G-values of the various SpA complexes had been calculated from hydrodynamic measurements. The theoretical decays clearly show that, even if phi G is much longer than phi F, these two rotational motions still cannot be resolved over the experimentally accessible time range. Families of emission anisotropy decay curves for IgG antibodies with different amounts of intrinsic global coupling and for anchored antibodies with different amounts of steric hindrance were simulated by varying the preexponential weighting factors of the flexible and global terms. By comparing the calculated curves with the measured decays, it is evident that the rabbit IgG anti-dansyl antibodies do not have much intrinsic global coupling, but rather they are highly flexible. The curves also indicate that even for the exceptionally compact IgG4-SpA2 17-S complex, which showed the most steric hindrance in electron micrographs, the appropriate phi G weighting factor is only 0.28. Thus, as supposed earlier, the anchored antibodies exhibit considerable segmental flexibility. In closing, the above concepts are used to examine the results of

Antigen-Antibody Complex

Conformational properties of adenylyl-3' leads to 5'-adenosine in aqueous solution.

A detailed 220-MHz NMR study has been made of the conformational properties for the homodinucleotide adenylyl-3' leads to 5'-adenosine, ApA, in D2O. Unambiguous signal assignments of all proton signals were made with the aid of selectively deuterated nucleotidyl units, ApA, ApA, and D-8ApA, and complete, accurate sets of NMR parameters were derived by simulation-iteration methods. Sets of limiting chemical shifts and coupling values were also obtained for ApA and constituent monomers 3'-AMP and 5'-AMP at infinite dilution and at identical ionization states for assessment of dimerization effects. Conformational properties were evaluated quantitatively for most of the conformational bonds of ApA and these are consistent with two compact folded dynamically averaged structures, a base-stacked right helical structure, I, characterized as anti, C3'-endo, g-, w,w' (320,330 degrees), g'g', gg, C3'-endo, anti, and a more loosely base-stacked loop structure, II, with anti, C3'-endo, g-, w,w' (80 degrees, 50 degrees), g'g', gg, C3'-endo, anti orientations. Dimerization produces a number of nucleotidyl conformational changes including a shift in ribose equilibrium C2'-endo (S) in equilibrium C3'-endo (N) in favor of C3'-endo in both Ap- and -pA (60:40 vs. 35:65 in monomers), a change in glycosidic torsion angle chiCN toward 0 degrees, and a greater locking-in of rotamers along bonds involved in the phosphodiester backbone. Moreover, there is clear evidence that the transitions from S leads to N forms and chiCN leads to 0 degrees are directly related to base stacking in ApA. Finally, ApA exists in solution as an equilibrium between I, II and an unstacked form(s) with as yet undetermined conformational features. Since C4'-C5', C5'-O5', and C3'-O3' bonds possess exceptional conformational stabilities, it is proposed that destacking occurs primarily by rotation about P-O5' and/or O3'-P. Predominant factors influencing the overall ApA conformation are thus base-base interaction and flexibility about P-O5' and O3'-P, with change of ribose conformation occurring in consequence of an alteration of chiCN, the latter in turn being governed by the need for maximum eta overlap of stacked adenine rings.

Adenine Nucleotides

A molecular dynamics simulation of polyalanine: an analysis of equilibrium motions and helix-coil transitions.

An understanding of helix dynamics can aid in interpreting the motions of proteins. The conformational transitions that occur also appear to play a role in protein folding. Structural studies of isolated peptides in solution are just becoming available. However, detailed analysis of the helix-coil transition is still not available and will be difficult to obtain experimentally. For these reasons, we performed a long molecular dynamics simulation of polyalanine at high temperature. Using this approach, we obtain a description of the overall structure and inherent flexibility of the chain as well as a structural picture of the conformational changes that occur. In this way, we can address both equilibrium properties of the peptide and the dynamics and mechanisms of the structural transitions. Our results correlate fairly well with the available experimental data and previous simulations aimed at addressing alpha-helix dynamics. The peptide spends the bulk of its time fluctuating between different conformations with intermediate helix contents. Transitions between highly ordered and highly disordered structures were rare, but they occurred rapidly. Our distribution of conformations favored collapsed states. Hence, our transitions to structures with high helical content were from fluctuating compact structures. The conversion between helix and coil occurred sequentially on a residue-by-residue basis. However, there was local cooperativity; the transition of a residue to the coil state was facilitated after a neighboring group became nonhelical. The relevance of our results to protein folding is also discussed.

Models, Chemical