Markus Christen

The GROMOS software for biomolecular simulation: GROMOS05

We present the latest version of the Groningen Molecular Simulation program package, GROMOS05. It has been developed for the dynamical modelling of (bio)molecules using the methods of molecular dynamics, stochastic dynamics, and energy minimization. An overview of GROMOS05 is given, highlighting features not present in the last major release, GROMOS96. The organization of the program package is outlined and the included analysis package GROMOS++ is described. Finally, some applications illustrating the various available functionalities are presented.

Architecture, implementation and parallelisation of the GROMOS software for biomolecular simulation☆

Abstract In this work the design of the latest version of the GROMOS software for biomolecular simulation, GROMOS11 is discussed. Detailed organisation and class descriptions of the MD++ simulation program and the GROMOS++ analysis package are given. It is shown how the code was documented, how it can be easily modified and extended, how debugging of it is carried out. Additional efficiency and parallelisation concepts are presented and benchmarked.

On searching in, sampling of, and dynamically moving through conformational space of biomolecular systems: A review

Methods to search for low‐energy conformations, to generate a Boltzmann‐weighted ensemble of configurations, or to generate classical‐dynamical trajectories for molecular systems in the condensed liquid phase are briefly reviewed with an eye to application to biomolecular systems. After having chosen the degrees of freedom and method to generate molecular configurations, the efficiency of the search or sampling can be enhanced in various ways: (i) efficient calculation of the energy function and forces, (ii) application of a plethora of search enhancement techniques, (iii) use of a biasing potential energy term, and (iv) guiding the sampling using a reaction or transition pathway. The overview of the available methods should help the reader to choose the combination that is most suitable for the biomolecular system, degrees of freedom, interaction function, and molecular or thermodynamic properties of interest.

Multigraining: An algorithm for simultaneous fine-grained and coarse-grained simulation of molecular systems

A method to combine fine-grained and coarse-grained simulations is presented. The coarse-grained particles are described as virtual particles defined by the underlying fine-grained particles are described as virtual particles defined by the underlying fine-grained particles. The contribution of the two grain levels to the interaction between particles is specified by a grain-level parameter lambda. Setting lambda = 0 results in a completely fine-grained simulation, whereas lambda = 1 yields a simulation governed by the coarse-grained potential energy surface with small contributions to keep the fine-grained covalently bound particles together. Simulations at different lambda values may be coupled using the replica-exchange molecular dynamics method to achieve enhanced sampling at the fine-grained level.

Deep Brain Stimulation in Parkinsonian Patients—Ethical Evaluation of Cognitive, Affective, and Behavioral Sequelae

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an important therapeutic advancement for the treatment of Parkinsons disease (PD). Its beneficial effects on motor functions are well established, but its cognitive, affective, and behavioral sequelae come increasingly into the focus of the medical and ethical discussion. In order to evaluate whether these side effects may counteract the beneficial effects of STN DBS on the patients quality of life, we classify them along the dimensions “measurement complexity” and “weighted life-impact.” Based on this analysis, we discuss their ethical impact and propose guidelines for the clinical setting of STN DBS.

Moral Intelligence – A Framework for Understanding Moral Competences

In light of several corporate ethical scandals and the financial crisis many people are asking what can be done to promote moral behavior and to prevent similar transgressions in the future. In this chapter, we argue that beyond cultural and contextual influences, changes do also require agents who are skilled in how to deal with moral issues and how to turn moral standards into actions. In order to specify the abilities that facilitate moral functioning, the present work is designed to put forth a theoretical framework of “Moral Intelligence” which integrates current literature and research on moral decision-making, social cognition and self-regulation theory. The framework’s elementary concepts (which are: the moral compass, moral commitment, moral sensitivity, moral problem solving and moral resoluteness) and the underlying mechanisms are detailed. At the end, the practical value of the advocated model and the question of how to enhance moral intelligence is also briefly discussed.

Dealing With Side Effects of Deep Brain Stimulation: Lessons Learned From Stimulating the STN

Deep brain stimulation (DBS) is increasingly investigated as a therapy for psychiatric disorders. In the ethical evaluation of this novel approach, incidence and impact of side effects (SE) play a key role. In our contribution, we analyze the discussion on SE of DBS of the subthalamic nucleus (STN)—a standard therapy for movement disorders like Parkinsons disease (PD)—based on 66 case reports, 69 review papers, and 347 outcome studies from 1993 to 2009. We show how the DBS community increasingly acknowledged the complexity of STN-DBS side effects. Then we discuss the issue of study quality and the methods used to assess SE. We note that some side effects are the subject of conflicting evaluations by the different stakeholders involved. This complicates the ethical controversy inherent in any novel treatments for diseases that involve psychiatric aspects. We delineate how the lessons from STN-DBS could guide future DBS applications in the field of psychiatry.

Measuring spike pattern reliability with the Lempel-Ziv-distance

Spike train distance measures serve two purposes: to measure neuronal firing reliability, and to provide a metric with which spike trains can be classified. We introduce a novel spike train distance based on the Lempel-Ziv complexity that does not require the choice of arbitrary analysis parameters, is easy to implement, and computationally cheap. We determine firing reliability in vivo by calculating the deviation of the mean distance of spike trains obtained from multiple presentations of an identical stimulus from a Poisson reference. Using both the Lempel-Ziv-distance (LZ-distance) and a distance focussing on coincident firing, the pattern and timing reliability of neuronal firing is determined for spike data obtained along the visual information processing pathway of macaque monkey (LGN, simple and complex cells of V1, and area MT). In combination with the sequential superparamagnetic clustering algorithm, we show that the LZ-distance groups together spike trains with similar but not necessarily synchronized firing patterns. For both applications, we show how the LZ-distance gives additional insights, as it adds a new perspective on the problem of firing reliability determination and allows neuron classifications in cases, where other distance measures fail.

On the Conformational Properties of Amylose and Cellulose Oligomers in Solution

Molecular dynamics (MD) simulations were used to monitor the stability and conformation of double-stranded and single-stranded amyloses and single-stranded cellulose oligomers containing 9 sugar moieties in solution as a function of solvent composition, ionic strength, temperature, and methylation state. This study along with other previous studies suggests that hydrogen bonds are crucial for guaranteeing the stability of the amylose double helix. Single-stranded amylose forms a helical structure as well, and cellulose stays highly elongated throughout the simulation time, a behavior that was also observed experimentally. In terms of coordination of solute hydroxyl groups with ions, amylose shows entropy-driven coordination of calcium and sulfate ions, whereas cellulose-ion coordination seems to be enthalpy-dominated. This indicates that entropy considerations cannot be neglected when explaining the structural differences between amyloses and celluloses.

How “moral” are the principles of biomedical ethics? – a cross-domain evaluation of the common morality hypothesis

BackgroundThe principles of biomedical ethics – autonomy, non-maleficence, beneficence, and justice – are of paradigmatic importance for framing ethical problems in medicine and for teaching ethics to medical students and professionals. In order to underline this significance, Tom L. Beauchamp and James F. Childress base the principles in the common morality, i.e. they claim that the principles represent basic moral values shared by all persons committed to morality and are thus grounded in human moral psychology. We empirically investigated the relationship of the principles to other moral and non-moral values that provide orientations in medicine. By way of comparison, we performed a similar analysis for the business & finance domain.MethodsWe evaluated the perceived degree of “morality” of 14 values relevant to medicine (n1 = 317, students and professionals) and 14 values relevant to business & finance (n2 = 247, students and professionals). Ratings were made along four dimensions intended to characterize different aspects of morality.ResultsWe found that compared to other values, the principles-related values received lower ratings across several dimensions that characterize morality. By interpreting our finding using a clustering and a network analysis approach, we suggest that the principles can be understood as “bridge values” that are connected both to moral and non-moral aspects of ethical dilemmas in medicine. We also found that the social domain (medicine vs. business & finance) influences the degree of perceived morality of values.ConclusionsOur results are in conflict with the common morality hypothesis of Beauchamp and Childress, which would imply domain-independent high morality ratings of the principles. Our findings support the suggestions by other scholars that the principles of biomedical ethics serve primarily as instruments in deliberated justifications, but lack grounding in a universal “common morality”. We propose that the specific manner in which the principles are taught and discussed in medicine – namely by referring to conflicts requiring a balancing of principles – may partly explain why the degree of perceived “morality” of the principles is lower compared to other moral values.