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Kevin Cahill

Publications and source records attributed to Kevin Cahill.

At least 37 records · Page 2Linked to original sources

Cell-Penetrating Peptides, Electroporation, and Drug Delivery

Certain short polycations, such as TAT and oligoarginine, rapidly pass through the plasma membranes of mammalian cells by a mechanism called transduction, as well as by endocytosis and macropinocytosis. These cell-penetrating peptides (CPPs) can carry with them cargos of 30 amino acids, more than the nominal limit of 500 Da and enough to be therapeutic. An analysis of the electrostatics of a charge outside the cell membrane and some recent experiments suggest that transduction may proceed by molecular electroporation. Ways to target diseased cells, rather than all cells, are discussed.

q-bio.BM↗

Molecular Electroporation and the Transduction of Oligoarginines

Certain short polycations, such as TAT and polyarginine, rapidly pass through the plasma membranes of mammalian cells by an unknown mechanism called transduction as well as by endocytosis and macropinocytosis. These cell-penetrating peptides (CPPs) promise to be medically useful when fused to biologically active peptides. I offer a simple model in which one or more CPPs and the phosphatidylserines of the inner leaflet form a kind of capacitor with a voltage in excess of 180 mV, high enough to create a molecular electropore. The model is consistent with an empirical upper limit on the cargo peptide of 40--60 amino acids and with experimental data on how the transduction of a polyarginine-fluorophore into mouse C2C12 myoblasts depends on the number of arginines in the CPP and on the CPP concentration. The model makes three testable predictions.

q-bio.BM↗

Computational Consequences of Neglected First-Order van der Waals Forces

We have computed the widely neglected first-order interaction between neutral atoms. At interatomic separations typical of condensed media, it is nearly equal to the 1/r^6 second-order London energy inferred from interactions in gasses. Our results, without the exchange forces that lead to covalent bonding, suggest that the quality of non-bonding attraction between neutral atoms of molecules in condensed media differs from the 1/r^6 form usually ascribed to it. If we add first-order and all second-order terms, we obtain energies nearly five times the 1/r^6 London energies which dominate only at the atomic separations found in gasses. For computation, we propose a practical, accurate form of energy to replace the qualitatively inaccurate Lennard-Jones and harmonic forms casually assumed to hold at the interatomic separations found in condensed media.

q-bio.BM↗

Parametrization of the Hybrid Potential for Pairs of Neutral Atoms

The hybrid form is a combination of the Rydberg potential and the London inverse-sixth-power energy. It is accurate at all relevant distance scales and simple enough for use in all-atom simulations of biomolecules. One may compute the parameters of the hybrid potential for the ground state of a pair of neutral atoms from their internuclear separation, the depth and curvature of their potential at its minimum, and from their van der Waals coefficient of dispersion.

q-bio.BM↗

Inflation in a Symmetric Vacuum

If in a finite universe, the tree-level vacuum is a symmetric superposition of coherent states, in each of which the inflaton field assumes a different, energy-minimizing mean value (vev), then the resulting energy is positive and decreases exponentially as the volume of the universe increases. This effect can drive inflation when that volume is small and explain part of dark energy when it is big, but the effect is exceedingly tiny except at very early times.

gr-qc↗

Rotations and Statistics

The way a field transforms under rotations determines its statistics--as is easy to see for scalar, Dirac, and vector fields.

hep-th↗

Learning about spin-one-half fields

It is hard to understand spin-one-half fields without reading Weinberg. This paper is a pedagogical footnote to his formalism with an emphasis on the boost matrix, spinors, and Majorana fields.

hep-th↗

Helices in Biomolecules

Identical objects, regularly assembled, form a helix, which is the principal motif of nucleic acids, proteins, and viral capsids.

q-bio.BM↗

Rydberg-London Potential for Diatomic Molecules and Unbonded Atom Pairs

We propose and test a pair potential that is accurate at all relevant distances and simple enough for use in large-scale computer simulations. A combination of the Rydberg potential from spectroscopy and the London inverse-sixth-power energy, the proposed form fits spectroscopically determined potentials better than the Morse, Varnshi, and Hulburt-Hirschfelder potentials and much better than the Lennard-Jones and harmonic potentials. At long distances, it goes smoothly to the correct London force appropriate for gases and preserves van der Waals's "continuity of the gas and liquid states," which is routinely violated by coefficients assigned to the Lennard-Jones 6-12 form.

q-bio.BM↗

Alternative Splicing and Genomic Stability

Alternative splicing allows an organism to make different proteins in different cells at different times, all from the same gene. In a cell that uses alternative splicing, the total length of all the exons is much shorter than in a cell that encodes the same set of proteins without alternative splicing. This economical use of exons makes genes more stable during reproduction and development because a genome with a shorter exon length is more resistant to harmful mutations. Genomic stability may be the reason why higher vertebrates splice alternatively. For a broad class of alternatively spliced genes, a formula is given for the increase in their stability.

q-bio.GN↗

Riemannian Gauge Theory and Charge Quantization

In a traditional gauge theory, the matter fields ϕ^a and the gauge fields A^c_μare fundamental objects of the theory. The traditional gauge field is similar to the connection coefficient in the Riemannian geometry covariant derivative, and the field-strength tensor is similar to the curvature tensor. In contrast, the connection in Riemannian geometry is derived from the metric or an embedding space. Guided by the physical principal of increasing symmetry among the four forces, we propose a different construction. Instead of defining the transformation properties of a fundamental gauge field, we derive the gauge theory from an embedding of a gauge fiber F=R^n or F=C^n into a trivial, embedding vector bundle F=R^N or F=C^N where N>n. Our new action is symmetric between the gauge theory and the Riemannian geometry. By expressing gauge-covariant fields in terms of the orthonormal gauge basis vectors, we recover a traditional, SO(n) or U(n) gauge theory. In contrast, the new theory has all matter fields on a particular fiber couple with the same coupling constant. Even the matter fields on a C^1 fiber, which have a U(1) symmetry group, couple with the same charge of +/- q. The physical origin of this unique coupling constant is a generalization of the general relativity equivalence principle. Because our action is independent of the choice of basis, its natural invariance group is GL(n,R) or GL(n,C). Last, the new action also requires a small correction to the general-relativity action proportional to the square of the curvature tensor.

hep-th↗

On the Kinematics of Protein Folding

We offer simple solutions to three kinematic problems that occur in the folding of proteins. We show how to construct suitably local elementary Monte Carlo moves, how to close a loop, and how to fold a loop without breaking the bond that closes it.

physics.bio-ph↗

Proteins Wriggle

We propose an algorithmic strategy for improving the efficiency of Monte Carlo searches for the low-energy states of proteins. Our strategy is motivated by a model of how proteins alter their shapes. In our model when proteins fold under physiological conditions, their backbone dihedral angles change synchronously in groups of four or more so as to avoid steric clashes and respect the kinematic conservation laws. They wriggle; they do not thrash. We describe a simple algorithm that can be used to incorporate wriggling in Monte Carlo simulations of protein folding. We have tested this wriggling algorithm against a code in which the dihedral angles are varied independently (thrashing). Our standard of success is the average root-mean-square distance (rmsd) between the alpha-carbons of the folding protein and those of its native structure. After 100,000 Monte Carlo sweeps, the relative decrease in the mean rmsd, as one switches from thrashing to wriggling, rises from 11% for the protein 3LZM with 164 amino acids (aa) to 40% for the protein 1A1S with 313 aa and 47% for the protein 16PK with 415 aa. These results suggest that wriggling is useful and that its utility increases with the size of the protein. One may implement wriggling on a parallel computer or a computer farm.

cond-mat.soft↗

Supersymmetry without Grassmann Variables

Supersymmetry transformations may be represented by unitary operators in a formulation of supersymmetry without numbers that anti-commute. The physical relevance of this formulation hinges on whether or not one may add states of even and odd fermion number, a question which soon may be settled by experiment.

hep-th↗

Toward a Neutrino Mass Matrix

One may identify the general properties of the neutrino mass matrix by generating many random mass matrices and testing them against the results of the neutrino experiments.

hep-ph↗

B-L Neutrinos

Neutrino masses and mixings are analyzed in terms of left-handed fields and a 6x6 complex symmetric mass matrix whose singular values are the neutrino masses. An angle theta_nu characterizes the kind of the neutrinos, with theta_nu=0 for Dirac neutrinos and theta_nu=pi/2 for Majorana neutrinos. At theta_nu = 0 baryon-minus-lepton number is conserved. If theta_nu is approximately zero, the six neutrino masses coalesce into three nearly degenerate pairs. Thus the tiny mass differences exhibited in the solar and atmospheric neutrino experiments are naturally explained by the approximate conservation of B-L. Neutrinos are nearly Dirac fermions. This B-L model leads to these predictions: neutrinos oscillate mainly between flavor eigenfields and sterile eigenfields, and so the appearance of neutrinos and antineutrinos is suppressed; neutrinos may well be of cosmological importance; in principle the disappearance of the tau neutrino should be observable; and neutrinoless double-beta decay is suppressed by an extra factor of 10^(-5) and so will not be seen in the Heidelberg/Moscow, IGEX, GENIUS, or CUORE experiments.

hep-ph↗

Neutrinos Are Nearly Dirac Fermions

Neutrino masses and mixings are analyzed in terms of left-handed fields and a 6x6 complex symmetric mass matrix whose singular values are the neutrino masses. An angle x_nu characterizes the kind of the neutrinos, with x_nu = 0 for Dirac neutrinos and x_nu = pi/2 for Majorana neutrinos. If x_nu = 0, then baryon-minus-lepton number is conserved. When x_nu is approximately zero, the six neutrino masses coalesce into three nearly degenerate pairs. Thus the smallness of the differences in neutrino masses exhibited in the solar and atmospheric neutrino experiments and the stringent limits on neutrinoless double beta decay are naturally explained if B-L is approximately conserved and neutrinos are nearly Dirac fermions. If one sets sin(x_nu) = 0.003, suppresses inter-generational mixing, and imposes a quark-like mass hierarchy, then one may fit the essential features of the solar, reactor, and atmospheric neutrino experiments with otherwise random mass matrices in the eV range. This B-L model leads to these predictions: neutrinos oscillate mainly between flavor eigenfields and sterile eigenfields, and so the probabilities of the appearance of neutrinos or antineutrinos are very small; neutrinos may well be of cosmological importance; in principle the disappearance of the tau neutrino should be observable; and neutrinoless double beta decay is suppressed by an extra factor of < 10^(-5) and hence will not be seen in the Heidelberg/Moscow, IGEX, GENIUS, or CUORE experiments.

hep-ph↗

Simulations of Protein Folding

We have developed a simple, phenomenological, Monte-Carlo code that predicts the three-dimensional structure of globular proteins from the DNA sequences that define them. We have applied this code to two small proteins, the villin headpiece (1VII) and cole1 rop (1ROP). Our code folds both proteins to within 5 A rms of their native structures.

hep-lat↗