PubMed Health⌕ Search

Biomedical subjects

Kazuhisa Nishizawa

Publications and source records attributed to Kazuhisa Nishizawa.

3 recordsLinked to original sources
PubMed2006

Interaction between K+ channel gate modifier hanatoxin and lipid bilayer membranes analyzed by molecular dynamics simulation.

Hanatoxin (HaTx) is an ellipsoidal-shaped peptide that binds to the voltage sensor of voltage-dependent channels. Of physicochemical interest, HaTx has a "ring" of charged residues around its periphery and a hydrophobic protrusion. It has previously been postulated that HaTx binds to and functions on the surface of membranes, but a recent fluorescent-quenching study has implied a fairly deep positioning of HaTx in the lipid bilayer membrane. We carried out numerous molecular dynamic simulations of HaTx1, a well-studied variant of HaTx, in fully hydrated phospholipid bilayers. The system reproduced the surface-binding mode of HaTx1, in which HaTx1 resided in the extracellular side (outer) of the water/membrane interface with the hydrophobic patch of HaTx1 facing the membrane interior. On the other hand, analyses with various parameter settings suggested that the surface-binding mode was unstable because of the substantial attractive electrostatic force between HaTx1 and the lipid head groups of the inner (opposite) leaflet. Compared with this electrostatic force, the energetic cost for membrane deformation involving meniscus formation appeared to be small. In an attempt to interpret the quenching data, we consider the possibility of dimpling (meniscus formation) that brings HaTx1 inward (only ~0.7-0.8 nm above the bilayer center), while accounting for the flexibility of both leaflets of the membrane and the long-range interaction between positively charged residues of the membrane-bound peptide and the polar head groups of the opposite leaflet of the membrane. It is suggested that molecular dynamics simulations taking into account the flexibility of the membrane surface is potentially useful in interpreting the fluorescence-quenching data.

Computer Simulation↗
PubMed2002

A DNA sequence evolution analysis generalized by simulation and the markov chain monte carlo method implicates strand slippage in a majority of insertions and deletions.

To study the mechanisms for local evolutionary changes in DNA sequences involving slippage-type insertions and deletions, an alignment approach is explored that can consider the posterior probabilities of alignment models. Various patterns of insertion and deletion that can link the ancestor and descendant sequences are proposed and evaluated by simulation and compared by the Markov chain Monte Carlo (MCMC) method. Analyses of pseudogenes reveal that the introduction of the parameters that control the probability of slippage-type events markedly augments the probability of the observed sequence evolution, arguing that a cryptic involvement of slippage occurrences is manifested as insertions and deletions of short nucleotide segments. Strikingly, approximately 80% of insertions in human pseudogenes and approximately 50% of insertions in murids pseudogenes are likely to be caused by the slippage-mediated process, as represented by BC in ABCD --> ABCBCD. We suggest that, in both human and murids, even very short repetitive motifs, such as CAGCAG, CACACA, and CCCC, have approximately 10- to 15-fold susceptibility to insertions and deletions, compared to nonrepetitive sequences. Our protocol, namely, indel-MCMC, thus seems to be a reasonable approach for statistical analyses of the early phase of microsatellite evolution.

Base Sequence↗