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Biomedical subjects

M Karplus

Publications and source records attributed to M Karplus.

At least 19 recordsLinked to original sources
PubMed1992

Beta-sheet coil transitions in a simple polypeptide model.

A simplified model of a polypeptide chain is used to study the dynamics of the beta-sheet-coil transition. Each amino acid residue is treated as a single quasiparticle in an effective potential that approximates the potential of mean force in solution. The model is used to study the equilibrium and dynamic aspects of the sheet-coil transition. Systems studied include ones with both strands free to move (two-strand sheet), and ones with either strand fixed in position (multistrand sheet). The equilibrium properties examined include sheet-coil equilibrium constants and their dependence on chain position. Dynamic properties are investigated by a stochastic simulation of the Brownian motion of the chain in its solvent surroundings. Time histories of the dihedral angles and residue-residue cross-strand distances are used to study the behavior of the sheet structure. Auto- and cross-correlation functions are calculated from the time histories with relaxation times of tens to hundreds of picoseconds. Sheet-coil rate constants of tens of ns-1 were found for the fixed strand cases.

Models, Molecular↗
PubMed1992

Simulation analysis of triose phosphate isomerase: conformational transition and catalysis.

A theoretical approach is employed to study the catalysis of the dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde 3-phosphate (GAP) reaction by the enzyme triose phosphate isomerase (TIM). The conformational change in a loop involved in protecting the active site from solvent is examined by use of X-ray data and molecular dynamics simulations. A mixed quantum-mechanics and molecular mechanics potential is used to determine the energy surface along the reaction path. The calculations address the role of the enzyme in lowering the barrier to reaction and provide a decomposition into specific residue contributions. To obtain a clearer understanding of the electronic effects, the polarization of the substrate carbonyl group by the active site residues is examined and compared with FTIR measurements on the wild-type and mutant forms of the enzyme.

Amino Acid Sequence↗
PubMed1992

[Surfactant replacement therapy for respiratory distress syndrome: a pilot study].

A pilot study of the effect of exogenous surfactant (ES) on premature infants with respiratory distress syndrome (RDS) is reported. Each of the first 15 infants in this study received 200 mg/kg of natural surfactant (Curosurf) during the first day of life. Controls were 56 infants with RDS seen in the 15 months prior to the study. Within 5 minutes of starting ES, in all infants there was rapid and dramatic improvement in oxygenation and improvement in the average arterial/alveolar ratio of 169%. They had lower oxygen and ventilatory requirements than the control group throughout the first 5 days of life. No treated infant suffered from pulmonary air leak, while in the control group 21% developed pneumothorax and 11% had pulmonary interstitial emphysema. Mortality was 13% in the treated group as compared to 27% in the control group (p less than 0.01). There were no differences between the groups in the incidence of sepsis, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, or bronchopulmonary dysplasia, nor were there side-effects of therapy. Dosage, timing and composition of the ideal surfactant are important questions for future studies.

Humans↗
PubMed1979

Side-chain torsional potentials: effect of dipeptide, protein, and solvent environment.

Side-chain torsional potentials in the bovine pancreatic trypsin inhibitor are calculated from empirical energy functions by use of the known X-ray structure of the protein and the rigid-geometry mapping technique. The potentials are analyzed to determine the roles and relative importance of contributions from the dipeptide backbone, the protein, and the crystalline environment of solvent and other protein molecules. The structural characteristics of the side chains determine two major patterns of energy surfaces, E(X1,X2): a gamma-branched pattern and a pattern for longer, straight side chains (Arg, Lys, Glu, and Met). Most of the dipeptide potential curves and surfaces have a local minimum corresponding to the side-chain torsional angles in the X-ray structure. Addition of the protein forces sharpens and/or selects from these minima, providing very good agreement with the experimental conformation for most side chains at the surface or in the core of the protein. Inclusion of the crystalline environment produces still better results, especially for the side chains extending away from the protein. The results are discussed in terms of the details of the interactions due to the surrounding, calculated solvent-accessibility figures and the temperature factors derived from the crystallographic refinement of the pancreatic trypsin inhibitor.

Animals↗
PubMed1979

Picosecond dynamics of tyrosine side chains in proteins.

To probe the details of small amplitude motions in proteins, a dynamical analysis of the orientation fluctuations of two tyrosine side chains in the bovine pancreatic trypsin inhibitor is presented. Detailed results are given for the time history and correlation functions obtained for the ring motion from a molecular dynamics simulation of the entire protein. It is shown that even on a picosecond time scale orientational fluctuations of +/-30 degrees from the average position occur for the tyrosine rings in the interior of the protein. It is found that the Langevin equation is applicable to the ring torsional motion, which corresponds to that of an angular harmonic oscillator with near-critical damping. Two possible microscopic models for the observed damping effects are outlined. One of these, analogous to liquid behavior, is based on kinetic theory and takes account of the collisions which occur between atoms of the protein; the other, more analogous to solid behavior, involves the coupling among a large number of harmonic oscillators. The collisional model with parameters obtained from theoretical estimates leads to good agreement with the correlation functions from the dynamic simulation. However, the dephasing of harmonic oscillations can yield similar short-time results so that a distinction between the two models is difficult. The importance of damping effects on the motions involved in conformational transitions and enzymatic reactions is discussed.

Animals↗
PubMed1979

Monosomy 21: a possible stepwise evolution of the karyotype.

We describe a female infant with manifestations of complete monosomy for chromosome 21 intrauterine growth retardation, failure to thrive, craniofacial anomalies, arthrogryposis-like features, and psychomotor retardation. Chromosome analysis demonstrated mosaicism for three different cell lines in the various tissues examined; 45,XX,-21/46,XX,del(21)(q11)46,XX. The existence of these three lines suggests a possible explanation for the few cases of "complete monosomy 21" which have been reported.

Abnormalities, Multiple↗
PubMed1979

Dynamics of activated processes in globular proteins.

A procedure for the dynamical simulation of activated processes, such as ligand binding and enzymatic reactions, in a globular protein is outlined. Preliminary calculations of the transition state geometry and barrier crossing trajectories are presented for a model reaction, the rotation of an aromatic ring in the bovine pancreatic trypsin inhibitor. The results show that repulsive nonbonded interactions between the ring atoms and the atoms in the surrounding protein matrix determine the dynamical character of the reorientation process; the nonbonded interactions are the source of the rotational barrier and of the impulses that speed up or slow down the ring motion during the barrier crossings.

Animals↗
PubMed1978

Lack of limb motor asymmetry in the neonate.

Neonates were examined for evidence of lateralization of motor function. The stepping test was done and the foot that moved first was recorded. The reaction of both arms to avoid an obstacle was also tested. No evidence for lateralization was found. Previous studies in the neonate have shown asymmetry of anatomical structures subserving language, and functional asymmetry of auditory functions and head position. However, the development of limb handedness occurs only at a later age.

Age Factors↗
PubMed1977

Dynamics of folded proteins.

The dynamics of a folded globular protein (bovine pancreatic trypsin inhibitor) have been studied by solving the equations of motion for the atoms with an empirical potential energy function. The results provide the magnitude, correlations and decay of fluctuations about the average structure. These suggest that the protein interior is fluid-like in that the local atom motions have a diffusional character.

Aprotinin↗