Biological simulations in drug discovery

Noble, Denis; Levin, Jeremy; Scott, William L.

doi:10.1016/s1359-6446(98)01277-x

Cited by 41 publications

(13 citation statements)

References 25 publications

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“…Given the complicated multifaceted nature of toxicity and pathological reactions, many kinds of pollutant-induced disease processes can only be effectively understood at the systems level, ranging from protein-protein interactions to the whole animal (Bonchev, 2003;Noble et al, 1999;Tarassov et al, 2008). Successful recognition of environmental disease syndromes depends to a large degree on an integrated understanding of the organism as a complex dynamic system (Noble et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Successful recognition of environmental disease syndromes depends to a large degree on an integrated understanding of the organism as a complex dynamic system (Noble et al, 1999). This argument can probably also be applied to the ''health" of biological assemblages and ecosystems.…”

Section: Introductionmentioning

confidence: 99%

“…This argument can probably also be applied to the ''health" of biological assemblages and ecosystems. Effective diagnosis of chemical pollutant impacts and predictions of their consequences requires that we have a capability to model biological interactions (Moore, 2002;Moore and Noble, 2004;Moore et al, 2006;Noble et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Is toxicological pathology characterised by a loss of system complexity?

Moore¹

2010

Marine Environmental Research

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Is toxicological pathology characterised by a loss of system complexity?

Moore¹

2010

Marine Environmental Research

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“…It is anticipated that models of human systems designed for drug discovery and development will dramatically improve the disappointingly low rate of successful verification of the medical effectiveness and safety of chemical compounds aimed at drug targets identified from genome sequences. The failures in this area have been attributed to the lack of biological insight accompanying sequence discoveries (Butcher 2005;Hood and Perlmutter 2004;Noble et al 1999). Bioremediation research informed by systems biology expects to integrate multiple levels of molecular and microorganismal interactions and design microbial systems able to remedy pollution in areas important to humans (Pazos et al 2003;Lovley 2003 successful it will be in its own right, there is no doubt that the quantity of data it is already integrating, and its emphasis on mathematical modelling of interacting molecules and their emergent properties, constitute a shift from earlier genomics and genetics approaches, as well as from earlier higher-level functional approaches such as physiology (Ideker et al 2006).…”

Section: Us and Japan (Us Department Of Energy 2005; Wtec Panel 2005;mentioning

confidence: 99%

The Study of Socioethical Issues in Systems Biology

O’Malley¹,

Calvert²,

Dupré³

2007

The American Journal of Bioethics

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Systems biology is the rapidly growing and heavily funded successor science to genomics. Its mission is to integrate extensive bodies of molecular data into a detailed mathematical understanding of all life processes, with an ultimate view to their prediction and control. Despite its high profile and widespread practice, there has so far been almost no bioethical attention paid to systems biology and its potential social consequences. We outline some of systems biology's most important socioethical issues by contrasting the concept of systems as dynamic processes against the common static interpretation of genomes. New issues arise around systems biology's capacities for in silico testing, changing cultural understandings of life, synthetic biology and commercialization. We advocate an interdisciplinary and interactive approach that integrates social and philosophical analysis and engages closely with the science. Overall, we argue that systems biology socioethics could stimulate new ways of thinking about socioethical studies of life sciences. KeywordsSystems biology, socioethics, genomics, bioethics, ELSI, genetics 2 The study of socioethical issues in systems biologySystems biology is the heir presumptive of the molecular advances made by genomics and associated high-throughput data gathering. Its mission is to integrate these extensive bodies of data into a detailed mathematical understanding of all life processes with an ultimate view to their prediction and control. Numerous governments have prioritized systems biology in their budgets for life science research and a rapidly growing body of literature identifies itself as systems biology. Despite its high profile and widespread practice, there has so far been almost no bioethical attention paid to systems biology and its potential social consequences. We will outline some of the most notable issues within a broad-ranging comparison of systems biology (including its claimed historical background and anticipated applications) with genomics and genetics and the

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“…However, in the field of biomedicine, simulation models of biological systems now contain sufficient detail not only to reconstruct normal functions but also to reconstruct major disease states. With the incorporation of the biochemical and biophysical properties of enzymes, receptors, membrane pumps and other gene products, the interactions of drugs and toxic xenobiotics (e.g., carcinogens and endocrine disrupters) with these cellular entities can be modelled and simulations of the action of drugs, organic toxins (xenobiotics) and toxic metal ions on normal cells and tissues can be attained (Noble et al 1999, Moore 2002a.…”

Section: Introductionmentioning

confidence: 99%

Editorial: Computational modelling of cell & tissue processes & function

Moore

Noble

2004

Histochem J

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Computational modelling of whole biological systems from cells to organs is gaining momentum in cell biology and disease studies. This pathway is essential for the derivation of explanatory frameworks that will facilitate the development of a predictive capacity for estimating outcomes or risk associated with particular disease processes and therapeutic or stressful treatments. This article introduces a series of invited papers covering a hierarchy of issues and modelling problems, ranging from crucial conceptual considerations of the validity of cellular modelling through to multi-scale modelling up to organ level. The challenges and approaches in cellular modelling are described, including the potential of 'in silico ' modelling applications for receptor-ligand interactions in cell signalling, simulated organ dysfunction (i.e., heart), human and environmental toxicity and the progress of the IUPS Physiome Project. A major challenge now facing biologists is how to translate the wealth of reductionist detail about cells and tissues into a real understanding of how these systems function and are perturbed in disease processes. In biomedicine, simulation models of biological systems now contain sufficient detail, not only to reconstruct normal functions, but also, to reconstruct major disease states. More widely, simulation modelling will aid the targeting of current 'knowledge gaps' and how to fill them; and also provide a research tool for selecting critical factors from multiple simulated experiments for real experimental design. The envisaged longer-term end- product is the creation of simulation models for predicting drug interactions and harmful side-effects; and their use in therapeutic and environmental health risk management. Finally, we take a speculative look at possible future scenarios in cellular modelling, where it is envisioned that integrative biology will move from being largely qualitative and instead become a highly quantitative, computer-intensive discipline.

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Biological simulations in drug discovery

Cited by 41 publications

References 25 publications

Is toxicological pathology characterised by a loss of system complexity?

Is toxicological pathology characterised by a loss of system complexity?

The Study of Socioethical Issues in Systems Biology

Editorial: Computational modelling of cell & tissue processes & function

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