Computer simulation of within family selection in finite populations

Summary The relative efficiency, in terms of selection limits, between mass selection and within family selection was compared by computer simulation methods. A 20-locus additive model was used to simulate a quantitative trait under selection. It was assumed that 50–75 percent of the genetic variance in the base population was controlled by four major genes initially at low frequencies.In populations of size N=100 no loss of major genes was found when either method of selection was used. When N=50 within family selection was generally superior to mass selection but when N=10 the situation was reversed. For N=30 within family selection was more efficient only under high selection intensity or high heritability situations.     

Computer simulation of mutagenesis

A FORTRAN program is described which simulates point-substitution mutations in the DNA strands of typical organisms. Its objective is to help students to understand the significance and structure of the genetic code, and the mechanisms and effects of mutagenesis. The program is intended to be used as part of an elementary course in genetics at degree level.     

Computer simulation of the segmental neural network generating locomotion in lamprey by using populations of network interneurons

Realistic computer simulations of the experimentally established local spinal cord neural network generating swimming in the lamprey have been performed. Populations of network interneurons were used in which cellular properties, like cell size and membrane conductance including voltage dependent ion channels were randomly distributed around experimentally obtained mean values, as were synaptic conductances (kainate/AMPA, NMDA, glycine) and delays. This population model displayed more robust burst activity over a wider frequency range than the more simple subsample model used previously, and the pattern of interneuronal activity was appropriate. The strength of the reciprocal inhibition played a very important role in the regulation of burst frequency, and just by changing the inhibitory bias the entire physiological range could be covered. At the lower frequency range of bursting the segmental excitatory interneurons provide stability as does the activation of voltage dependent NMDA receptors. Spike frequency adaptation by means of summation of afterhyperpolarization (AHP) serves as a major burst terminating factor, and at lower rates the membrane properties conferred by the NMDA receptor activation. The lateral interneurons were not of critical importance for the burst termination. They may, however, be of particular importance for inducing a rapid burst termination during for instance steering and righting reactions. Several cellular factors combine to provide a secure and stable motor pattern in the entire frequency range.     

Computer simulation of DNA supercoiling

We treat supercoiled DNA within a wormlike model with excluded volume. A modified Monte Carlo approach has been used, which allowed computer statistical-mechanical simulations of moderately and highly supercoiled DNA molecules. Even highly supercoiled molecules do not have a regular shape, though with an increase in writhing the chains look more and more like branched interwound helixes. The averaged writhing (Wr) approximately 0.7 delta Lk. The superhelical free energy F is calculated as a function of the linking number. Lk. The calculations have shown that the generally accepted quadratic dependence of F on Lk is valid for a variety of conditions, though it is by no means universal. Significant deviations from the quadratic dependence are expected at high superhelical density under ionic conditions where the effective diameter of DNA is small. The results are compared with the available experimental data.     

Computer simulation of single-file transport

A stochastic model of single-file transport was developed as the Markov process in continuous time technique. The model was constructed using an EC-1060 computer. Unidirectional fluxes were investigated and populations of channels were correlated with flux fluctuations. The profiles of channel populations were shown to have nonlinear shapes even with the transport of nonelectrolyte (the classical diffusion approach gives linear profiles). The relationship between the paired correlation function F(AB) and the concentration of transported particles was examined. The F(AB) profile was shown to become flattened (or exponential for asymmetrical cases) at high concentrations. The concentration dependence jA/jA0 ratio were analyzed, where jA is a single-file unidirectional flux, jA0 is unidirectional flux for the case of free diffusion. An interesting "stack" phenomenon was observed for abnormal time correlations of single-file fluxes.     

Computer simulation of introductory neurophysiology

A computer-assisted learning (CAL) package, NeuroLab, developed for use by first-year university students undertaking professional programs in the health area, is described and evaluated. NeuroLab is a simulation of a laboratory, in which students are able to impale neurons to measure resting membrane potentials and subsequently undertake experiments including measuring resting membrane potentials, determining threshold potentials, measuring refractory periods, and examining effects on membrane potential through altering the membrane permeability to sodium and potassium ions. Students find the package to be a worthwhile learning experience, with 81 +/- 2.2% reporting the package increased their understanding of neuron function, and 78 +/- 2.5% expressing a desire for more CAL packages. Exposure to the package resulted in significantly higher mean scores in a multiple-choice question test on measuring neuron membrane potentials compared with those who were not exposed (mean scores out of 4 of 2.42 and 2.02, respectively, P < 0.001).     

Computer simulation of purine metabolism

A computer model of purine metabolism, including catabolism, salvage pathways and interconversion among nucleotides, is given. Steady-state rate equations corresponding to metabolic enzymes are written based on information from the literature about their kinetic behaviour. Numerical integration of this set of equations is performed employing selected parameters taken from the literature. After stabilization of purine compound concentrations is reached, simulation of enzyme deficit and enzyme overproduction is carried out. The latter is calculated by varying specified maximum velocities in the numerical integration. A pattern of intermediate metabolite concentrations is found. These results form a basis for the comparison of normal patterns or patterns reflecting the effects of inborn errors of metabolism. The aim of this paper is to demonstrate the usefulness of this computer simulation method in complex metabolism pathways.     

Computer simulation of biological systems

The current status of mathematical models of biological systems is reviewed. Advances in supercomputer hardware allows more complex models to be constructed. The new generation of microcomputers are quite adequate for many computer simulations of biological systems. A theory of modeling is being developed to improve the relationship between the real biological system and the model. Deterministic models, stochastic models and applications of control theory and optimization methods are discussed. Examples given include models of molecular structure, of experimental techniques, and of biochemical reactions. It is recommended that experimental biologists consider the use of microcomputers to model the system under study as a part of their research program.     

Computer simulation of calcium-induced myotonia

Summary In an extensive research project on myotonia, the ionic mechanisms which are at the basis of the phenomenon of calcium-induced myotonia have been taken into consideration. A mathematical model of a muscle fibre was constructed to demonstrate the possibility that anomalous values of the membrane permeability to Calcium ions have an active part in the genesis of myotonia. This work was in great part supported by Grant of Muscular Dystrophy Assoc. Inc. and by CNR, Rome.     

Robustness and regularity of oscillations in neuronal populations

We study a biologically plausible but computationally simplified integrate-and-fire neuronal model. Oscillatory activity is analyzed in the networks with and without self-connections. We perform a detailed scan of four major parameters that represent the properties of neurons and synapses: connection ratio, connection strengths, post-synaptic potential decay rate and soma's potential decay rate. It is observed that networks with different properties exhibit different periods and different patterns of synchrony. We find that generally these oscillations are robust against changes of parameters, meanwhile we also locate the parametric boundaries where oscillations break down.     

Computer simulation of movement-generating cross-bridges.

A stochastic computational method was developed to study properties of cross-bridge models for muscle contraction, by following the time history of individual cross-bridge model of Andrew Huxley (1957) and a modified two-state model with more realistic behavior during steady stretching are used as examples. The method can readily compute steady-state force during shortening and stretching and force-transients following rapid changes in length. Computations of velocity with a steady load and of velocity transients are more sensitive to the randomness inherent in the stochastic method.     

Computer simulation of antibody binding specificity

A Monte Carlo algorithm that searches for the optimal docking configuration of hen egg white lysozyme to an antibody is developed. Both the lysozyme and the antibody are kept rigid. Unlike the work of other authors, our algorithm does not attempt to explicitly maximize surface contact, but minimizes the energy computed using coarse-grained pair potentials. The final refinement of our best solutions using all-atom OPLS potentials (Jorgensen and Tirado-Rives⁸) consistently yields the native conformation as the preferred solution for three different antibodies. We find that the use of an exponential distance-dependent dielectric function is an improvement over the more commonly used linear form. © 1993 Wiley-Liss, Inc.     

Computer simulation of renal countercurrent systems

The history of mathematical modeling of renal countercurrent systems is briefly outlined. Several examples are cited and discussed. These include efforts at parameter estimation and experimental design with models. The goal of this work was the evaluation of hypotheses of hypertonic urine formation. The argument is made that computer simulation with reasonably isomorphic models can be used in a variety of ways, but that one indispensable role for this approach is to provide a test of the quantitative sufficiency of hypotheses. Hypotheses of hypertonic urine formation that do not consider active transport in thin ascending limbs do not pass this test. A new proposal is suggested in which the energy for NaCl reabsorption from thin ascending limbs is derived from dissipation of a urea gradient via an antiport.     

Computer simulation of human body dynamics

Understanding human body dynamics is important in many situations, such as automobile and aircraft crashes, aircraft ejections, falls, and other acceleration environments. The design of automobile interiors, cockpits, and safety equipment requires knowledge of the forces and accelerations encountered during an emergency. Because of the limited information available from actual events and the various constraints in testing, computer simulations are often the only means of obtaining detailed information. The Armstrong Laboratory (AL) developed the Articulated Total Body (ATB) model to predict the human body dynamics in many of these environments. This model is a three-dimensional rigid body dynamics program in which the human body is modeled as a series of segments. Forces on the body segments are calculated based on their interaction with the surroundings including seat and cockpit surfaces. The model also calculates the internal joint resistive and constraint forces. Because of this capability to predict both internal and external forces acting on the body, the ATB model can be used in investigating injuries. It is also a valuable design tool for evaluating safety of proposed systems before prototypes are built or costly tests conducted. When testing is conducted, the model provides data that cannot be measured, such as forces within the body, and supplementing test data with parameter variation simulations. To validate the model, tests such as those conducted on the AL impact sled are simulated. Test films and instrumentation data are compared with simulation graphics and quantitative output to gain confidence in the simulation results.     

Computer simulation of protein molecular dynamics

A review of the works on the computer simulation of the globular protein dynamics is given. Methodological aspects of the simulation procedure are outlined briefly. Main peculiarities of protein dynamics revealed in the course of simulation of pancreatic trypsin inhibitor and cytochrome c are presented. The causes of "anomalous" processes, inherent in the simulated behaviour of model proteins are discussed. These "anomalous" processes are: continuous drift of the structure and its deviation from the experimental one, determined by X-ray analysis. Both processes are supposed to be the consequence of the reduced conformational rigidity of the model protein in comparison to the real one. Among the possible reasons for this reduced rigidity absence of the water molecules, hydrating peptide groups in the real protein, may be mentioned. Analogy between "anomalous" processes in the simulated protein dynamics and some phenomena observed in the real proteins during their functioning is drawn.     

Computer simulation of Paramecium chemokinesis behavior

A computer program was designed to simulate the distribution of paramecia in a T-maze assay for chemo-accumulation and dispersal. Simulated values of chemokinesis are compared to experimental values for normal and mutant paramecia. The roles of components of swimming behavior (turning frequency and swimming speed), adaptation, and reaction at the border of solutions are examined.