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Biomedical subjects

D A Case

Publications and source records attributed to D A Case.

64 records · Page 4Linked to original sources
PubMed1986

Dynamic simulations of oxygen binding to myoglobin.

We report dynamic simulations of the process by which a dioxygen molecule enters or leaves the heme pocket region of myoglobin along a path between the distal histidine (E7) and valine (E11). Our reaction coordinate measures the distance of the ligand from a "dividing plane" defined by three protein atoms. The equilibrium probability distribution as a function of this coordinate is determined by a series of molecular-dynamic simulations with overlapping "umbrella" constraining potentials; the resulting potential of mean force has a barrier of about 7 kcal/mol for exit from the heme pocket. A comparison of this free energy profile with the corresponding potential energy profile suggests that entropy effects dominate the kinetic barrier. Reactive trajectories are generated from dynamic simulations beginning at the top of the potential of mean force; only a small fraction of these recross the dividing surface, indicating that transition state theory may be a good approximation for this process.

Computer Simulation↗
PubMed1985

Human observing: maintained by negative informative stimuli only if correlated with improvement in response efficiency.

Two experiments investigated the effect of observing responses that enabled college students to emit more efficient distributions of reinforced responses. In Experiment 1, the gains of response efficiency enabled by observing were minimized through use of identical low-effort response requirements in two alternating variable-interval schedules. These comprised a mixed schedule of reinforcement; they differed in the number of money-backed points per reinforcer. In each of three choices between two stimuli that varied in their correlation with the variable-interval schedules, the results showed that subjects preferred stimuli that were correlated with the larger average amount of reinforcement. This is consistent with a conditioned-reinforcement hypothesis. Negative informative stimuli--that is, stimuli correlated with the smaller of two rewards--did not maintain as much observing as stimuli that were uncorrelated with amount of reward. In Experiment 2, savings in effort made possible by producing S- were varied within subjects by alternately removing and reinstating the response-reinforcement contingency in a mixed variable-interval/extinction schedule of reinforcement. Preference for an uncorrelated stimulus compared to a negative informative stimulus (S-) decreased for each of six subjects, and usually reversed when observing permitted a more efficient temporal distribution of the responses required for reinforcement; in this case, the responses were pulls on a relatively high-effort plunger. When observing the S- could not improve response efficiency, subjects again chose the control stimulus. All of these results were inconsistent with the uncertainty-reduction hypothesis.

Attention↗
PubMed1983

Human observing: Maintained by stimuli correlated with reinforcement but not extinction.

College students received points exchangeable for money (reinforcement) on a variable-time 60-second schedule that alternated randomly with an extinction component. Subjects were informed that responding would not influence either the rate or distribution of reinforcement. Instead, presses on either of two levers ("observing responses") produced stimuli. In each of four experiments, stimuli positively correlated with reinforcement and/or stimuli uncorrelated with reinforcement were each chosen over stimuli correlated with extinction. These results are consistent with prior results from pigeons in supporting the conditioned-reinforcement hypothesis of observing and in not supporting the uncertainty-reduction hypothesis.

Journal Article↗
PubMed1981

The delay-reduction hypothesis of conditioned reinforcement and punishment: Observing behavior.

Pigeons responded in an observing-response procedure in which three fixed-interval components alternated. Pecking one response key produced food reinforcement according to a mixed schedule. Pecking the second (observing) key occasionally replaced the mixed-schedule stimulus with the stimulus correlated with the fixed-interval component then in effect. In Experiment 1, observing was best maintained by stimuli correlated with a reduction in mean time to reinforcement. That finding was consistent with the conditioned-reinforcement hypothesis of observing behavior. However, low rates of observing were also maintained by stimuli not representing delay reduction. Experiment 2 assessed the role of sensory reinforcement. It showed that response rate was higher when maintained by stimuli uncorrelated with reinforcement delay than when the stimuli were correlated with a delay increase. This latter result supports a symmetrical version of the conditioned-reinforcement hypothesis that requires suppression by stimuli correlated with an increase in time to reinforcement. The results were inconsistent with hypotheses stressing the reinforcing potency of uncertainty reduction.

Journal Article↗
PubMedDate not supplied

Theory and applications of the generalized Born solvation model in macromolecular simulations.

Generalized Born (GB) models provide an attractive way to include some thermodynamic aspects of aqueous solvation into simulations that do not explicitly model the solvent molecules. Here we discuss our recent experience with this model, presenting in detail the way it is implemented and parallelized in the AMBER molecular modeling code. We compare results using the GB model (or GB plus a surface-area based "hydrophobic" term) to explicit solvent simulations for a 10 base-pair DNA oligomer, and for the 108-residue protein thioredoxin. A slight modification of our earlier suggested parameters makes the GB results more like those found in explicit solvent, primarily by slightly increasing the strength of NH [bond] O and NH [bond] N internal hydrogen bonds. Timing and energy stability results are reported, with an eye toward using these model for simulations of larger macromolecular systems and longer time scales.

Computer Simulation↗
PubMedDate not supplied

Langevin modes of macromolecules: applications to crambin and DNA hexamers.

Langevin modes describe the behavior of atoms moving on a harmonic potential surface subject to viscous damping described by a classical Langevin equation. We present applications to the protein crambin and to the DNA duplex d(CpGpCpGpCpG)2 and its complex with ethidium. Our friction matrix is weighted according to surface area exposed to solvent, and results are reported for various values of the solvent viscosity and models for hydrodynamic interactions. Even for relatively small solvent friction (eta = 0.3 cp) a substantial number of modes are overdamped, and time correlation functions decay smoothly without the oscillations characteristic of gas-phase calculations. Perturbation theory starting from the gas-phase modes is accurate for many low-frequency modes (which are overdamped in the presence of solvent), but fails badly for higher modes. For correlation functions of interest to fluorescence depolarization or nmr relaxation, the plateau values are insensitive to solvent viscosity, but the relaxation times are not. The advantages and limitations of this analysis of macromolecular motions are discussed.

DNA↗