This paper presents a case of severe uncertainty in the development of autonomous and intelligent systems in Artificial Intelligence and autonomous robotics. After discussing how uncertainty emerges from the complexity of the systems and their interaction with unknown environments, the paper describes the novel framework of explorative experiments. This framework presents a suitable context in which many of the issues relative to uncertainty, both at the epistemological level and at the ethical one, in this field should be reframed. The case (...) of autonomous robot systems for search and rescue is used to make the discussion more concrete. (shrink)

Researchers often pursue proof of concept research, but criteria for evaluating such research remain poorly specified. This article proposes a general framework for proof of concept research that k...

In the late 19th century, physiologists such as David Ferrier, Eduard Hitzig, and Hermann Munk argued that cerebral brain functions are localized in discrete structures. By the early 20th century, this became the dominant position. However, another prominent physiologist, Friedrich Goltz, rejected theories of cerebral localization and argued against these physiologists until his death in 1902. I argue in this paper that previous historical accounts have failed to comprehend why Goltz rejected cerebral localization. I show that Goltz adhered to a (...) falsificationist methodology, and I reconstruct how he designed his experiments and weighted different kinds of evidence. I then draw on the exploratory experimentation literature from recent philosophy of science to trace one root of the debate to differences in how the German localizers designed their experiments and reasoned about evidence. While Goltz designed his experiments to test hypotheses about the functions of predetermined cerebral structures, the localizers explored new functions and structures in the process of constructing new theories. I argue that the localizers relied on untested background conjectures to justify their inferences about functional organization. These background conjectures collapsed a distinction between phenomena they produced direct evidence for (localized symptoms) and what they reached conclusions about (localized functions). (shrink)

Model organisms are a living form of scientific models. Despite the widespread use of model organisms in scientific research, the actual representational relationship between model organisms and their target species is often poorly characterized in the context of cross-species research. Many model organisms do not represent the target species adequately, let alone accurately. This is partly due to the complex and emergent life phenomena in the organism, and partly due to the fact that a model organism is always taken to (...) represent a broad range of diverse organisms. More often than not, model organisms are taken as a reference point for an extrapolation to be made to the unknown characteristics of other species. I propose to view model organisms as analogue simulators which represent the emergent phenomenon in the context of cross-species research. A model organism represents a wide range of species by simulating their molecular microstates which underlie various emergent phenomena. I show that although model organisms represent the target species inadequately at many levels of complexity, they have epistemic values as a simulator in virtue of which the emergent phenomenon can be modeled dynamically, a virtue that is hardly attainable by non-dynamic models. (shrink)

Traditional frameworks for evaluating scientific models have tended to downplay their exploratory function; instead they emphasize how models are inherently intended for specific phenomena and are to be judged by their ability to predict, reproduce, or explain empirical observations. By contrast, this paper argues that exploration should stand alongside explanation, prediction, and representation as a core function of scientific models. Thus, models often serve as starting points for future inquiry, as proofs of principle, as sources of potential explanations, and as (...) a tool for reassessing the suitability of the target system. This is illustrated by a case study of the varied career of reaction-diffusion models in the study of biological pattern formation, which was initiated by Alan Turing in a classic 1952 paper. Initially regarded as mathematically elegant, but biologically irrelevant, demonstrations of how, in principle, spontaneous pattern formation could occur in an organism, such Turing models have only recently rebounded, thanks to advances in experimental techniques and computational methods. The long-delayed vindication of Turing’s initial model, it is argued, is best explained by recognizing it as an exploratory tool. (shrink)

1. Overview and organizing themes 2. Historical Review: Aristotle to Mill 3. Logic of method and critical responses 3.1 Logical constructionism and Operationalism 3.2. H-D as a logic of confirmation 3.3. Popper and falsificationism 3.4 Meta-methodology and the end of method 4. Statistical methods for hypothesis testing 5. Method in Practice 5.1 Creative and exploratory practices 5.2 Computer methods and the ‘third way’ of doing science 6. Discourse on scientific method 6.1 “The scientific method” in science education and as seen (...) by scientists 6.2 Privileged methods and ‘gold standards’ 6.3 Scientific method in the court room 6.4 Deviating practices 7. Conclusion Bibliography Academic Tools Other Internet Resources Related Entries . (shrink)

We employ a pragmatic model of inquiry to distinguish the epistemological character of exploratory experimentation. Exploratory experimentation is not constituted by any intrinsic characteristics of an episode of experimentation but depends on the context and aims of the experiment and the ways in which these shape decisions about how the experimental inquiry is to be conducted: its tasks, resources, and aims, as well as the critical assessment of all of these. To demonstrate the usefulness of our pragmatist model, we apply (...) it to the contrast between two kinds of searches for new physics at the Large Hadron Collider. Some searches are exploratory while others target specific Beyond Standard Model hypotheses, but this contrast can be understood only by considering the relations between these searches, their aims, and the way that these aims shape their respective experimental parameters and procedures. Our approach provides a model for establishing the epistemological significance of details of experimental practice. (shrink)

Experimental modeling in biology involves the use of living organisms (not necessarily so-called "model organisms") in order to model or simulate biological processes. I argue here that experimental modeling is a bona fide form of scientific modeling that plays an epistemic role that is distinct from that of ordinary biological experiments. What distinguishes them from ordinary experiments is that they use what I call "in vivo representations" where one kind of causal process is used to stand in for a physically (...) different kind of process. I discuss the advantages of this approach in the context of evolutionary biology. (shrink)

The aim of this work is to elucidate John F. W. Herschel’s distinctive contribution to nineteenth-century British inductivism by exploring his understanding of experimental methods. Drawing on both his explicit discussion of experiment in his Preliminary Discourse on Natural Philosophy and his published account of experiments he conducted in the domain of electromagnetism, I argue that the most basic principle underlying Herschel’s epistemology of experiment is that experiment enables a particular kind of lower-level experimental understanding of phenomena. Experimental practices provide (...) knowledge of a particular phenomenon as a genuine effect produced under precise material conditions whose connections with other phenomena can be traced by variations in experimental parameters. The orienting concern of experimental inquiry seems to be the production of a secure understanding of phenomena even if it has no direct theoretical significance. Insofar as one can generate this lower-level understanding, it can function both as a fertile source for explanatory principles about phenomena and as a body of evidence against which one can test the adequacy of an explanatory hypothesis. This project provides evidence of Herschel’s inductivism not merely as a philosophical approach to understanding the sciences but as a methodological commitment in scientific practice. (shrink)

I describe two traditions of philosophical accounts of evidence: one characterizes the notion in terms of signs of success, the other characterizes the notion in terms of conditions of success. The best examples of the former rely on the probability calculus, and have the virtues of generality and theoretical simplicity. The best examples of the latter describe the features of evidence which scientists appeal to in practice, which include general features of methods, such as quality and relevance, and general features (...) of evidence, such as patterns in data, concordance with other evidence, and believability of the evidence. Two infamous episodes from biomedical research help to illustrate these features. Philosophical characterization of these latter features—conditions of success—has the virtue of potential relevance to, and descriptive accuracy of, practices of experimental scientists. (shrink)

The discovery and ongoing investigation of microRNAs suggest important conceptual and methodological lessons for philosophers and historians of biology. This paper provides an account of miRNA research and the shift from viewing these tiny regulatory entities as minor curiosities to seeing them as major players in the post-transcriptional regulation of genes. Conceptually, the study of miRNAs is part of a broader change in understandings of genetic regulation, in which simple switch-like mechanisms were reinterpreted as aspects of complex cellular and genome-wide (...) processes. Among them are the activities of small RNAs, previously regarded as non-functional. Methodologically, the miRNA story suggests new ways of characterizing biological research that should prove helpful to philosophers of science who seek to develop more pluralistic, pragmatic models of scientific inquiry. miRNA research displays iterative movements between multiple modes of investigation that include not only the proposal and testing of hypotheses but also exploratory, technology-oriented and question-driven modes of research. As an exemplary story of scientific discovery and development, the miRNA case illustrates transitions from genetics to genomics and systems biology, and it shows how diverse configurations of research practice are related to major scientific advances. (shrink)

The chemical characterization of the substance responsible for the phenomenon of “transformation” of pneumococci was presented in the now famous 1944 paper by Avery, MacLeod, and McCarty. Reception of this work was mixed. Although interpreting their results as evidence that deoxyribonucleic acid (DNA) is the molecule responsible for genetic changes was, at the time, controversial, this paper has been retrospectively celebrated as providing such evidence. The mixed and changing assessment of the evidence presented in the paper was due to the (...) work’s interpretive flexibility – the evidence was interpreted in various ways, and such interpretations were justified given the neophytic state of molecular biology and methodological limitations of Avery’s transformation studies. I argue that the changing context in which the evidence presented by Avery’s group was interpreted partly explains the vicissitudes of the assessments of the evidence. Two less compelling explanations of the reception are a myth-making account and an appeal to the wartime historical context of its publication. (shrink)

This paper explores multiple experimental interventions in molecular biology. By “multiple,” we mean that molecular biologists often use different modes of experimental interventions in a series of experiments for one and the same subject. In performing such a series of experiment, scientists may use different modes of interventions to realize plural goals such as testing given hypotheses and exploring novel phenomena. In order to illustrate this claim, we develop a framework of multiple modes of experimental interventions to analyze a series (...) of experiments for a single subject. Our argument begins with a brief characterization of Craver and Darden’s taxonomy of experiments, because the taxonomy they have made implies various modes of interventions. We propose to extract two interventional directions and two interventional effects from their taxonomy as the basis of classification. The vertical or inter-level direction means that an intervention is performed between different levels of organization and the horizontal or inter-stage direction means that an intervention is performed between different stages of a mechanism. Interventions may produce an excitatory or an inhibitory effect. As a consequence, we can classify modes of interventions according to different directions and effects. We illustrate our claims by doing a case study of the PaJaMo experiment, which is a series of experiments for a single subject. The final goal in this paper is to provide a taxonomy of characteristics of experimentation in which the PaJaMo experiment is adequately located. (shrink)

To explain their role in discovery and contrast them with theory-driven research, philosophers of science have characterized exploratory experiments in terms of what they lack: namely, that they lack direction from what have been called “local theories” of the target system or object under investigation. I argue that this is incorrect: it’s not whether or not there is direction from a local theory that matters, but instead how such a theory is used to direct an experiment that matters. Appealing to (...) contemporary exploratory experiments that involve the use of experimental techniques—specifically, examples where scientists explore the interaction of neural activity and human behavior by magnetically stimulating brains—I argue that local theories of a target system can inform auxiliary hypotheses in exploratory experiments, which direct these experiments. These examples illustrate how local theories can direct the exploration of target systems where researchers do not aim to evaluate these theories. (shrink)

Exploratory inquiry has difficulty attracting research funding because funding agencies have little sense of how to detect good science in exploratory contexts. After documenting and explaining the focus on hypothesis testing among a variety of institutions responsible for distinguishing between good and bad science, I analyze the NIH grant review process. I argue that a good explanation for the focus on hypothesis testing—at least at the level of science funding agencies—is the fact that hypothesis-driven research is relatively easy to appraise. (...) I then explore one method by which we might gauge the epistemic merits of different styles of inquiry. (shrink)

In this article, I focus on the role of computer simulations as exploratory strategies. I begin by establishing the non-theory-driven nature of simulations. This refers to their ability to characterize phenomena without relying on a predefined conceptual framework that is provided by an implemented mathematical model. Drawing on Steinle’s notion of exploratory experimentation and Gelfert’s work on exploratory models, I present three exploratory strategies for computer simulations: (1) starting points and continuation of scientific inquiry, (2) varying the parameters, and (3) (...) scientific prototyping. (shrink)

Exploratory experiments are widely characterized as experiments that do not test hypotheses. Experiments that do test hypotheses are characterized as confirmatory experiments. Philosophers have pointed out that research programmes can be both confirmatory and exploratory. However, these definitions preclude single experiments being characterized as both exploratory and confirmatory; how can an experiment test and not test a hypothesis? Given the intuition that some experiments are exploratory, some are confirmatory, and some are both, a recharacterization of the relationship between exploratory and (...) confirmatory experimentation is needed. I discuss ‘phase IV’ trials to show what this recharacterization could look like. Phase IV trials can be exploratory and confirmatory insofar as they concurrently test hypotheses and explore for unforeseen phenomena. Even if it is uncontroversial that a single experiment can have multiple aims, the recharacterization of the relationship between exploratory and confirmatory experimentation is still required for these aims to be held together coherently. I offer an alternative characterization of the relationship between exploratory and confirmatory experimentation where the former remains a distinct kind of experimentation but is not characterized as non-hypothesis-testing. (shrink)

The work of Gaston Bachelard is known for two crucial concepts, that of the epistemological rupture and that of phenomenotechnique. A crucial question is, however, how these two concepts relate to one another. Are they in fact essentially connected or must they be seen as two separate elements of Bachelard’s thinking? This paper aims to analyse the relation between these two Bachelardian moments and the significance of the concept of phenomenotechnique for today. This will be done by examining how the (...) concepts of Bachelard have been used from the 1960s on. From this historical perspective, one gets the impression that these two concepts are relatively independent from each other. The Althusserian school has exclusively focused on the concept of ‘epistemological break’, while scholars from Science & Technology Studies, such as Bruno Latour, seem to have only taken up the concept of phenomenotechnique. It in fact leads to two different models of how to think about science, namely the model of purification and the model of proliferation. The former starts from the idea that sciences are rational to the extent that they are purified and free from obstacles. Scientific objectivity, within this later model, is not achieved by eradicating all intermediaries, obstacles and distortions, but rather exactly by introducing as many relevant technical mediators as possible. Finally, such a strong distinction will be criticized and the argument will be made that both in Bachelard’s and Latour's thought both concepts are combined. This leads to a janus-headed view on science, where both the element of purification and the element of proliferation are combined. (shrink)

My aim in this article is to introduce readers to the topic of exploratory experimentation and briefly explain how the three articles that follow, by Richard Burian, Kevin Elliott, and Maureen O'Malley, advance our understanding of the nature and significance of exploratory research. I suggest that the distinction between exploratory and theory-driven experimentation is multidimensional and that some of the dimensions are continuums. I point out that exploratory experiments are typically theory-informed even if they are not theory-driven. I also distinguish (...) between research programs and experiments. Research programs that are largely exploratory, such as the ones discussed in these case studies, can involve both exploratory and theory-driven experimentation. (shrink)

This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate the importance (...) of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only important for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion. (shrink)

The 1980s, it is often claimed, was the decade when experimentation finally became a philosophical topic. This was the responsibility, the claim continues, of one particular movement within philosophy of science, called “new experimentalism.” The aim of this article is to complicate this historical narrative. We argue that in the 1980s, the study of experimentation was carried out not by one movement with one particular aim but rather in a diverse and open-ended way by people with different aims and backgrounds. (...) We then argue that from the late 1990s onward, this diversity disappeared and made room for disciplinary divisions—questions concerning experimentation became philosophical, others sociological, and so on. The reason for this, we claim, was that science and technology studies, philosophy of technology, and philosophy of science took over aspects of the 1980s study of experimentation. In this way, we argue, these elements became institutionalized, whereas others were forgotten. The importance of this process of institutionalization is illustrated by means of a discussion of other, similar approaches to the philosophy of experimentation that have not been able to ensure continuity because they did not find an institutional home. (shrink)

Driven by an appreciation of the field’s early stage of development, I apply the concept of exploratory experimentation, originally put forward in the late 90s philosophy of biology, to current research in cognitive neuroscience. I concentrate on functional magnetic resonance imaging and how this wide-spread technique is used, from experimental design to data analysis. I claim that, although subject to certain significant modifications with respect to the concept’s original rendering, the exploratory character of neuroimaging experiments can be appreciated considering their (...) goals, centered on the stabilization of experimental systems for phenomenological description, and the relevance of their methodological facet. Although I do not claim that there is a specific kind of experiment that one can single out as definitely exploratory, exploration can be seen as a general trait imbuing fMRI-based experimentation. (shrink)

The standard view in current philosophy of creativity says that being creative has two requirements: being novel and being valuable. The standard view on creativity has recently become an object of critical scrutiny. Hills and Bird have specifically proposed to remove the value requirement from the definition, as it is not clear that creative objects are necessarily valuable or creative people necessarily praiseworthy. In this paper, I argue against Hills and Bird, since eliminating the element of value from the explanation (...) of creativity hinders the understanding of the role that creative products play in actual epistemic practices, which are fundamentally normative. More specifically, I argue that the terms ‘creativity’ and ‘creative’ function as thick epistemic concepts when employed by competent epistemic agents in practice, that is, these concepts have both a descriptive and an evaluative content that cannot be disentangled from one another. Accordingly, I suggest that philosophers should prefer thick accounts over thin accounts of creativity. A thick account of creativity is one that endorses the standard view at its basis, but further develops it in two ways: by stressing the entanglement of the value and novelty requirements; by permitting to encompass a range of domain-specific characterizations of such entanglement for different epistemic situations. In order to take the first steps in the development of such a thick account of creativity, I look at the domain of scientific practices as a case in point, and try to spell out what the thickness of creative instances typically entails here. Namely, I identify the worthy novelty of creative models and methods with their potential to clarify a tradition, with fruitfulness, and with the fulfilment of exploratory aims. (shrink)

The life sciences are said to be in the midst of a replication crisis because a majority of published results are irreproducible, and scientists rarely replicate existing data. Here I argue that point 2 of this assessment is flawed because there is a hitherto unidentified form of replication in the experimental life sciences, which I call ‘microreplications’. Using a case study from biochemistry, I illustrate how MRs depend on a key element of experimentation, namely, experimental controls. I end by reflecting (...) on what MRs mean for the broader debate about the replication crisis. (shrink)

In this paper, I propose an account that accommodates the possibility of experimentation being exploratory in cases where the procedures necessary to plan and perform an experiment are dependent on the theoretical accounts of the phenomena under investigation. The present account suggests that experimental exploration requires the implementation of an exploratory procedure that serves to extend the range of possible outcomes of an experiment, thereby enabling it to pursue its objectives. Furthermore, I argue that the present account subsumes the notion (...) of exploratory experimentation, which is often attributed in the relevant literature to the works of Friedrich Steinle and Richard Burian, as a particular type of experimental exploration carried out in the special cases where no well-formed theoretical framework of the phenomena under investigation exists. I illustrate the present account in the context of the ATLAS experiment at CERN’s Large Hadron Collider, where the long-sought Higgs boson has been discovered in 2012. I argue that the data selection procedure carried out in the ATLAS experiment illustrates an exploratory procedure in the sense suggested by the present account. I point out that this particular data selection procedure is theory-laden in that its implementation is crucially dependent on the theoretical models of high energy particle physics which the ATLAS experiment is aimed to test. However, I argue that the foregoing procedure is not driven by the above-mentioned theoretical models, but rather by a particular data selection strategy. I conclude that the ATLAS experiment illustrates that, contrary to what previous studies have suggested, there are cases of experimentation in which exploration serves to test theoretical predictions and that theory-ladenness plays an essential role in experimentation being exploratory. (shrink)

A number of scholars have recently drawn attention to the importance of iteration in scientific research. This paper builds on these previous discussions by drawing a distinction between epistemic and methodological forms of iteration and by clarifying the relationships between them. As defined here, epistemic iteration involves progressive alterations to scientific knowledge claims, whereas methodological iteration refers to an interplay between different modes of research practice. While distinct, these two forms of iteration are related in important ways. Contemporary research on (...) the biological effects of nanomaterials illustrates that methodological iteration can help to “initiate,” “equip,” and “stimulate” epistemic iteration. (shrink)

This chapter offers a review of standard views about the requirements for natural selection to shape evolution and for the sorts of ‘units’ on which selection might operate. It then summarizes traditional arguments for genic selectionism, i.e., the view that selection operates primarily on genes (e.g., those of G. C. Williams, Richard Dawkins, and David Hull) and traditional counterarguments (e.g., those of William Wimsatt, Richard Lewontin, and Elliott Sober, and a diffuse group based on life history strategies). It then offers (...) a series of responses to the arguments, based on more contemporary considerations from molecular genetics, offered by Carmen Sapienza. A key issue raised by Sapienza concerns the degree to which a small number of genes might be able to control much of the variation relevant to selection operating on such selectively critical organs as hearts. The response to these arguments suggests that selection acts on many levels at once and that sporadic selection, acting with strong effects, can act successively on different key traits (and genes) while maintaining a balance among many potentially conflicting demands faced by organisms within an evolving lineage. (shrink)

Signature-based model-independent searches for new physics form an explorative component of High Energy Physics experiments that aims at avoiding biases toward beyond-the-standard-model theo...

ArgumentIn the theory-dominated view of scientific experimentation, all relations of theory and experiment are taken on a par; namely, that experiments are performed solely to ascertain the conclusions of scientific theories. As a result, different aspects of experimentation and of the relations of theory to experiment remain undifferentiated. This in turn fosters a notion of theory-ladenness of experimentation (TLE) that is toocoarse-grainedto accurately describe the relations of theory and experiment in scientific practice. By contrast, in this article, I suggest that (...) TLE should be understood as anumbrella conceptthat has different senses. To this end, I introduce a three-fold distinction among the theories of high-energy particle physics (HEP) as background theories, model theories, and phenomenological models. Drawing on this categorization, I contrast two types of experimentation, namely, “theory-driven” and “exploratory” experiments, and I distinguish between the “weak” and “strong” senses of TLE in the context of scattering experiments from the history of HEP. This distinction enables identifying the exploratory character of the deep-inelastic electron-proton scattering experiments – performed at the Stanford Linear Accelerator Center (SLAC) between the years 1967 and 1973 – thereby shedding light on a crucial phase of the history of HEP, namely, the discovery of “scaling,” which was the decisive step towards the construction of quantum chromo-dynamics as a gauge theory of strong interactions. (shrink)

Along three measurements at the Large Hadron Collider (LHC), a high energy particle accelerator, we analyze procedures and consequences of exploratory experimentation (EE). While all of these measurements fulfill the requirements of EE: probing new parameter spaces, being void of a target theory and applying a broad range of experimental methods, we identify epistemic differences and suggest a classification of EE. We distinguish classes of EE according to their respective goals: the exploration where an established global theory cannot provide the (...) details of a local phenomenon, exploration of an astonishing discovery and exploration to find a new entity. We find that these classes also differ with respect to the existence of an identifiable target and their impact on the background theory. The characteristics distinguish EE from other kinds of experimentation, even though these different kinds have not yet been systematically studied. The formal rigor and precision of LHC physics facilitates to analyze concept formation in its early state. In particular we emphasize the importance for nil–results for conceptualization and argue that conceptualization can also be achieved from nil–results only. (shrink)

Data production in experimental sciences depends on localised experimental systems, but the epistemic properties of data transcend the contingencies of the processes that produce them. Philosophers often believe that experimental systems instantiate but do not produce the epistemic properties of data. In this paper, we argue that experimental systems' local functioning entails intrinsic capacities to produce the epistemic properties of data. We develop this idea by applying Derrida's model of arche-writing to study a case of theory-oriented experimental practice. Derrida's model (...) relativises or dissolves the conceptual distinction between the moment of data production and a subsequent moment of data dissemination. It thus has consequences for understanding both data production (despite being intrinsically local, data production a priori generates transferrable and modellable information) and data dissemination (when modelling information, researchers needs to refer this information to the context of its production). We study a case of data production in a non-exploratory experimental system designed to test a pre-existing hypothesis in visual neuroscience. A case of theory-oriented experimental practice should allow us to identify the autonomous functioning of experimental systems in data production more clearly, insofar as it allows us to study the limits of pre-existing theory in the activities of these systems. We suggest that pre-existing concepts, hypotheses and theories condition the relevance but not the production of experimental data. (shrink)

Computational modeling is one of the primary approaches to constructing protein–protein interfaces in the laboratory. The algorithm-driven computational protein design has been successfully applied to the construction of functional proteins with improved binding affinity and increased thermostability. It is intriguing how a computational protein modeling approach can construct and shape the reality of new functional proteins from scratch. I articulate an account of abstraction and exploration-driven strategies in this computational endeavor. I aim to show that how a computational modelling approach, (...) which is laden with mathematics and algorithms, can have a constructive force on the target protein. (shrink)